re

le Dr

r ms limartn retoryor in

contribution of importantrecepbiologych, assive evolvingy repr

actionave be

teristics, ferrocene versus nickelocene and the saturated aldehydehomologous series.

When nature nds a useful theme, it is usually made use ofrepeatedly. For example, consider functional groups: amide

(protein), acetal (carbohydrate), ester (lipid), the steroid skeleton(hormones) and the isoprene unit (terpenes and natural rubber), aswell as reaction processes, such as, involvement of electrostatics,

Compounds, such as hydrogen, nitrogen and oxygen, with nodipoles have no odors, in accord with the theoretical framework.Chlorine reacts rapidly at the receptor to produce odorous material.These molecules were also included in the Vibration theory [10].Alkanes have quite small dipoles, e.g. propane (DM 0.08) (Table 1)[13] and relatively weak odors. Natural gas (methane) is dilutedwith a strong odorant in order to aid in leak detection. On the otherhand, common perfumes contain functional groups (aldehyde,

* Tel.: 1 619 5945595; fax: 1 619 5944634.

Contents lists available at

Journal of Ele

.e l

Journal of Electrostatics 70 (2012) 1e6E-mail address: pkovacic@sundown.sdsu.edu.controversy. The Shape approach appears to have lost favor overthe years. A 2002 book provides extensive limitations [12].However, there can be no doubt that shape plays a crucial role inreceptor binding, an important aspect of the overall process. As anelaboration of earlier suggestions, widespread data for the Vibra-tion Theory was presented, based mainly on inelastic electrontunneling spectroscopy [10,11]. Some of the salient features consistof studies on enantiomers, deuterated materials, unusual correla-tions with thiols and boranes involving odor and spectral charac-

electrochemical events in the cerebral olfactory cortex. Theunifying approach is able to rationalize most of the elements in thevibration proposal, in addition to providing novel insight. Theframework is interdisciplinary based on interaction of elementsknown to play vital roles in living systems. Since action mode isoften multifaceted, other factors may also participate.

2. Part A. odorant molecules and dipoles: limited correlation1. Introduction

Recent reviews document theinvolvement of the combination ofelectrochemistry in many aspects ofis reasonable to apply this approamechanism of scent based on extenhas been considerable research involfactory system, the proposed theormechanistic framework.

The two principal prior modes ofMolecular Vibrations [10,11]. Both h0304-3886/$ e see front matter 2011 Published bydoi:10.1016/j.elstat.2011.07.005tors, cell signaling andand medicine [1e9]. Itan extension, to the

idence. Although therethese elements in theesents a novel, unifying

are based on Shape anden the object of much

electron transfer, enzymes, cell signaling and reactive oxygenspecies. The literature is rife with examples. The Vibration theory isanalogous to themode of action of sight and hearing which also canbe regarded as spectral senses [10]. Hence, application to smell isnot alone. The Electrochemical theory can be devided into fourparts: (A) limited correlation of odor with dipole moments (DMs)and electrostatic elds (EFs), (B) receptor binding followed byinteraction of the ligand EF with EFs of the receptor protein, (C)interaction of the modied EF with the olfactory nerve, and (D)Review

Mechanism of smell: Electrochemistry,

Peter Kovacic*

Department of Chemistry and Biochemistry, San Diego State University, 5500 Campani

a r t i c l e i n f o

Article history:Received 15 December 2010Accepted 21 July 2011Available online 25 October 2011

Keywords:ScentMechanismElectrochemistryNeuronsCell signalingReceptor

a b s t r a c t

This report presents in fousignaling. In Part A, there ields (EFs), and odor. For PEF with those of the proteithe altered EF to the olfacconverted to perceived od

journal homepage: wwwElsevier B.V.ceptors and cell signaling

ive, San Diego, CA, USA

ain parts a novel approach based on electrochemistry, receptors and cellited correlation between dipole moments (DMs), associated electrostatic

B, binding of the odorant to the receptor results in interaction of the ligandceptor, resulting in alteration. Part C addresses passage of the message byneurons. Part D represents the nal step in which the electrical signal isthe cerebral olfactory cortex.

2011 Published by Elsevier B.V.

SciVerse ScienceDirect

ctrostatics

sevier .com/locate/elstat

lectrketone, ester and nitrile) possessing higher DM values (1.75e3.92)(Table 1). However, this relationship alone is not sufcient inrationalizing the experimental data. The possible involvement ofdipoles was briey considered in the Vibration theory article:.one might expect there to be some relationship between atomicpartial charges and the strength of an odorant. Especially, this is thecase:.groups such as ketones, nitro groups, aldehyde, nitriles andether links are all polar groups. This, however, cannot be the solereason for differences in odor strength. For example, vanillin is oneof the strongest odorants known, whereas the closely relatedheliotropin is much weaker despite similar partial charges [10].The notion that the smell of a molecule is the sum of its parts [11]can be interpreted as the sum of the EFs from the electrostaticstandpoint. The next section provides a rationale based on theeffect of binding to receptors on altering the molecular dipoles.

A criticism of both Vibration and Electrochemistry theories isthat vibrational energies can be small as in the case with somedipole forces (EFs) of odorant molecules. Is there sufcient energyto produce the observed result? Electrostatic forces can be rela-tively weak for dipoles, but stronger for ions. However a 2008article questions the validity of that argument. Can such low levelshave an inuence in living systems? A recent study providesevidence for involvement. Investigators have gained insight intophysiological events in which weak forces, as low as 0.5 pN, playa regulatory role [e.g., in ion channel functioning [14] and DNAsynthesis [15]]. The effect of small forces was studied on partici-

Table 1Dipole moments of organic functional groups [13].

Compound Dipole moment (DM)

Propane 0.08cis-2-Butene 0.25Diethyl ether 1.10Ethylamine 1.22Phenol 1.22Dimethyl sulde 1.55Ethanethiol 1.60Ethanol 1.69Acetic acid 1.70Ethyl acetate 1.75Chloromethane 1.89Pentaborane 2.13Acetaldehyde 2.75Acetone 2.88Acetamide 3.68Acetonitrile 3.90

P. Kovacic / Journal of E2pation of four-armed DNA structures in DNA recombination.Signicant impact on the conformational structures was made byforces as weak as 0.5 pN. Therefore, it is reasonable to conclude thatelectrostatic energetics can play a role in biological processes, assuggested in our various reviews [1e9], as well as molecularvibrations.

3. Part B. interaction of odor molecule EF with receptor EFs

An appropriate introduction to this section is the following:The discovery of smell receptors owes almost everything to thetenacity and intuition of a single scientist, Linda Buck. Her work,published in 1991 caused the hitherto largely stagnant eld of smellresearch to burst into renewed life [11].

It is evident that the EFs alone of molecules are insufcient torationalize the experimental observations. However, docking of themolecule into the receptor site brings the molecular EFs in contactwith EFs of the receptor protein. There are many protein EFs ofvarying strengths associated with the numerous functionalitiespresent. Some of the functional groups possess strong EFs, as withthe ions derived from acidic and basic amino acids. The mostprevalent dipole and a strong one (DM 3.68) (Table 1) is that ofthe peptide (amide) bond. Alterations can occur with interactionsof dipoles or ions in the receptor, hydrogen bonding, ion formationwith volatile acids and bases and covalent bonding. Thus, mole-cules with identical DMs and EFs can have different odors sincebinding to different receptors results in different EFs due to variedalteration. The important aspect of change in the strength of theodorant molecule EF eld has received scant attention previously.The altered EF then propagates the sequence by interaction withneurons in the olfactory system.

There is considerable information concerning the olfactoryreceptors. In the mammalian olfactory system, information fromapproximately 1000 different odorant receptor types is organizedinto four spatial zones [16]. Each zone is a mosaic of randomlydistributed neurons expressing different receptor types. In theolfactory bulb, the information undergoes organization intoa spatial map. The discriminatory capacity of the mammalianolfactory system is such that thousands of volatile chemicals areperceived as having distinct odors [17]. Odorant receptors (ORs)were identied for molecules with related structures, but variedodors. One OR recognizes multiple odorants and one odorant isrecognized by multiple ORs, but different odorants are recognizedby different combinations of ORs. Thus, the olfactory system usesa combinatorial receptor coding scheme to encode odor identities.Slight alterations in an odorant or a concentration change, can alterits code.

The spatial distribution of odorant receptor RNAs in the mouseolfactory epithelium were examined [18]. Topographically distinctpatterns exist of receptor RNAs suggesting that the nasal cavity isdivided into a series of expression zones. The zonal patterning mayserve as initial organizing steps in an olfactory sensory informationcoding. Molecular electrostatic potential derived from repeatingphosphate groups in RNA may be a contributing factor. Thedetection of chemically distinct odorants presumably results fromthe association of odorous ligands with specic receptors onolfactory sensory neurons [19]. A novel gene family may encodediverse groups of odorant receptors. In a review, in mammals,olfactory stimuli are detected by sensory neurons located at twodistinct sites: the olfactory epithelium (OE), located at the posteriornasal cavity, and the vomeronasal organ (VNO), a tubular structurethat opens into the nasal cavity [20]. Whereas volatile odorants aredetected in the OE, the VNO may be specialized to detect phero-mones. Sensory signals generated in both cases are transmittedthrough different neural pathways in the brain. OE-derived signalsreach higher cortical centers, whereas those from the VNO aretargeted to the amygdala and hypothalamus. Each neuron appearsto express a single receptor type. Neurons expressing the samereceptor are randomly distributed on one of four spatial zones inthe OE. However, in the olfactory bulb, the axons of these neuronsconverge on only a few stereotyped glomeruli. Like odorantreceptors, the VNO counterparts may be G-protein coupled. In theOE, it appears that each odorant receptor may recognize a partic-ular structural feature shared by many odorants and that eachodorant may be recognized by many different receptors. Accordingto the electrochemical theory, .a particular structural featureshared by many odorants might be electrostatic elds associatedwith the receptor-ligand complexes.

The review also addresses aspects of cell signaling. If differentreceptors expressed by the same cell transduce signals via differenttransduction pathways, they may function independently. Theremay be crosstalk among different pathways that might providea basis for the integration and processing of sensory informationwithin an individual chemosensory neuron. An olfactory neuron-

ostatics 70 (2012) 1e6specic G-protein was identied strengthening the case for

lectra G-protein coupled mechanism of olfactory transduction [21].Different neurons respond to different odorants, a presumedrequirement for odor discrimination. Information from differentolfactory receptors is organized in the nose as well as the next relayin the olfactory system, the olfactory cortex.

4. Part C. receptor-ligand dipolar interaction with olfactoryneurons

The principal basis consists of electrochemical interaction of thereceptor-ligand EF with the olfactory neurons. Representative,supporting literature is summarized. Ion gradients are the source ofelectrical potentials in neurons [22]. The impulses that are carriedalong axons, as signals passing fromneuron to neuron, are electricalin nature. These electrical signals occur as transient change in theelectrical potential differences (voltages) across the membrane ofneurons. Such potentials are generated by ion gradients. Nerveimpulses, also called action potentials, are transient changes in themembrane potential that move rapidly along nerve cells. Actionpotentials are created when the membrane is locally depolarized.These small changes are enough to have a dramatic effect onspecic proteins in the axon membrane called voltage-gated ionchannels. Various electrochemical interactions occur with theneuron system. According to the olfactory approach, EFs arisingfrom interaction of the odorant EF with the receptor EFs then passthe message onto the olfactory neurons in step C of the sequence.

4.1. Electro-olfactograms

Research quite relevant to the electrochemical approachinvolves electro-olfactograms (EOGS) which reect electricalpotentials of the olfactory epithelium that occur in reference to theolfactory stimulation [23]. The EOG represents the sum of thegenerator potentials of olfactory receptor neurons. This approachhas been used extensively with animals, together with a muchlesser application to humans. A review outlines the following: (a)the cellular and physiological nature of the EOG response, (b) odorselection and delivery and (c) application of the EOG in humans,sh and insect olfaction and pheromonal responsivity [24]. Thetrout EOG by amino acids was a monophasic negative voltagecomposed of a phasic component which declined to a steady level[25]. A related report deals with responses to mixtures of aminoacids [26]. Results suggest that when odors are carried by a gentlewind, the air movement induces EOG oscillations and modulatesynthetic spike patterning of olfactory outputs to the secondaryolfactory relay center [27,28]. Oscillatory potential changes super-imposed on the typical EOG were observed in toads during thebreeding season [29]. The potentials were also observed from theolfactory nerve of the brain. After chemical stimulation of thehuman olfactory epithelium, it is possible to record a negativeresponse in the EOGwhich is interpreted as the summated receptorpotentials of the olfactory nerve [30]. Data conrm that kinetics ofthe cellular processes that underlie the EOG are slowed by Narisocclusion [31]. The character of changes andmaximumdecreases ofthe EOG amplitude after olfactory nerve axotomy varied in differentparts of the olfactory organ [32].

An article discusses molecular mechanisms of the sense of smelland taste [33]. Emphasis is on the transformation into electricalsignals. This important contribution, which has received scantattention, adds credibility to the electrochemical theme. In theinitial process of chemoreception, a stimulatory substance absorbsonto a membrane. The olfactory cells are primary sensory cellsconnected to the end of the olfactory nerve, and they depolarizewhen a stimulating substance absorbs in a receptive membrane.

P. Kovacic / Journal of EHence, an impulse is generated directly from the nerve withoutinvolvement of a synapse. The olfactory nerves can be viewed asinformation converters for changing chemical information intoelectrical signals. Therefore, a large resting potential which isnegative inside the cell is produced. If the nerve is stimulated, thesodium channel opens and the ions outside ow inside. Opening ofthe channel greatly lowers membrane resistance. The potentialchange makes the inside more positive. The receptor potential ofthe olfactory cell is fundamentally the same as that of the gustatorycell. The membrane potential change occurs in the presence ofvarious types of stimulants. When a stimulant is absorbed on thesurface of olfactory cells, the membrane potential changes. There isa change in the membrane conformation resulting in alteration inthe arrangement of charge transfer complexes and dipoles of themembranes resulting in change of membrane potential. In livingolfactory cells, membrane resistance is lowered when receptorpotential is generated. Since olfactory cells are part of the olfactorynerve, the value of membrane resistance should include resistanceat the impulse generating position. The change in membranepotential is propagated by electrons to the synapse region orimpulse generating position. In a report evaluating function anddisorders of smell, the following comments were made:.methods are objective which record post-stimulatory electro-physiological events at different steps of olfactory pathways. Theelectric response olfactometry representing a cortical evoked so-called twin-potential containing equivalents for the trigeminaland olfactory sense activity starts to demonstrate its efciency[34]. An electro-behavioral study was performed of limbic seizuresoriginating in the olfactory bulb [35].

The above important investigations clearly demonstrate theparticipation of bioelectrochemistry in the olfactory processentailing response to binding with the receptor.

4.2. External electrical stimulus

An appreciable amount of attention has been paid to exposure ofthe olfactory system to external electrical stimulus. The results arein accord with an electrochemical approach to olfactory action.

Electrical stimulation of the human olfactory mucous was per-formed by means of an electrode [14,36]. The stimulations did notevoke the sensation of smell, but suppressed smell sensations ofpresented odorants. When stimulation followed exposure to anodorant, the stimulus recalled the faded sensation of the precedingodorant. Animals were trained to associate the presence of an odorwith the electric shocks [37]. Most adult studies on aversivelearning with Drosophila employed electric shock as a negativeenforcer [38]. The research involved odor-electric shock learning inthe larva and adult. In electric stimulation studies, action potentialsin the olfactory nerve were associated with short-duration, rapidlydepolarizing optical responses in the nerve layer [39]. There arevarious other investigations on the electrical stimulus topic[40e49].

Although the electrical stimulus and the odor molecule bothprovide electrochemical force, the stimulus is different in havingmobile electrons as the source. Also, interaction of the externalstimulus with the olfactory nerve is not the same as for the odormolecule.

5. Part D. cerebral olfactory cortex

Since the brain is replete with electrochemical activity, it is notsurprising that extensive, relevant literature pertains to the olfac-tory cortex [50]. This part of the cerebrum receives sensory inputfrom the olfactory bulb. Initially, a G-protein is stimulated whichtriggers enzymatic conversion of ATP to cAMP, a secondmessenger,

ostatics 70 (2012) 1e6 3followed by activity in membrane channels. The events cause

studies [64e68]. Evidence for the presence of eNOS in mammalianolfactory sensory neurons and its involvement in odor adaptationimplicates nitric oxide as an important new element in the olfac-tory signal transduction [69]. The activating effects of odorantsappear to be mediated via different G-proteins [70]. Thus, at leasttwo different second messenger pathways seem to be involved in

increase the response signal for detecting ligand binding. These

remain conned in the odds [12]. The physical difference might

lectrostatics 70 (2012) 1e6membrane charge to become more positive, or depolarize, whichtravels down the axon of the olfactory receptor cells to the olfactorynerve. There is considerable literature documenting electricaleffects in the cerebral olfactory cortex. Slices of the guinea pigswere used to compare the potency of various Ca-channel blockerson the electrophysiology of synaptic transmission [51]. Listed inorder of potency, the divalent cations of Cd, Ni, Mn, Co and Mgdepressed synaptic transmission. Verapanil and diltiazendepressed both synaptic transmission and action potential. Anelectrophysiological study was made of the degeneration of theafferent axons of the lateral olfactory tract which gives rise toexcitatory synapses throughout the olfactory cortex of the guineapig [52]. Potential changes between the pial and cut surfaces ofslices of guinea pig olfactory cortex produced by gamma-aminobutyric acid were recorded with the electrodes [53]. Thereare other related reports [54e58].

6. Electron transfer

It is well established that ET processes play important roles inbiology and medicine [59]. The negative electron in motion createsan electric eld that can interact with others.

Reviews discuss involvement of ET with receptor binding [5,59].Hence one can imagine participation of ET in the electrochemicalphenomena taking place in the olfactory system. A book alsotouches upon the aspect [12]: The [receptor] gap nicely accom-modates all molecules (at best those up to 10 wide), and as themolecule slots into it, suddenly the electrons have before thema bridge reaching from the in side to the out side, and they hurlthemselves across this bridge. This bridging aspect in receptor,ligands and ET has been discussed by others [5,59]. ET commonlyoccurs in the receptor protein [59]. A report discusses the roleplayed by EFs, such as those associated with the dipolar peptidebond. The ions and positive or negative dipoles interact with thenegative electron involved in ET.

7. Cell signaling

Cell signaling (signal transduction) plays an important role inbiology and medicine, in which there is involvement of electro-chemical effects [1e9]. Animals, including humans, can be regardedas complex electrochemical systems which evolved over billions ofyears. Organisms interacted with and adapted to an environment ofelectrical and magnetic elds. Humans are now immersed ina man-made atmosphere of such elds whose long-term effects areunknown. The reviews provide much evidence linking cellsignaling with electrical effects, including ET. There is considerableliterature dealing with electrochemical effects associated with cellsignaling in the olfactory system, providing further support for thetheoretical framework. Investigations of vertebrate signal trans-duction reveal that calcium-gated chloride channels are activatedduring odorant detection in the chemosensory membrane ofolfactory sensory neurons [60]. This activation leads to depolar-ization of the membrane voltage and can induce electrical excita-tion. Molecular signaling underlines the response of the olfactorysensory neurons [61]. A signal transduction cascade leads toopening of ion channels, generating a current that leads into thecilia and depolarizes the membrane. Interaction between odorantand receptor initiates olfactory signal transduction that producesa cation inux and change in the membrane potential of theolfactory sensory neuron [62]. Stimulation of the odorant cellsresults in a calcium inux that activates the transduction pathway[63]. Ca acceptors, such as calmodulin, may mediate between thechange in intracellular Ca and the conductance mechanism

P. Kovacic / Journal of E4underlying the initial electrical event. There are a number of relatedresult in differences in EF interaction between the odd and the evenodorants and receptor proteins. Both thiols (DM 1.60) andboranes (DM 2.13) have relatively high dipole moments (Table 1).

9. Other aspects

In contrast to other theories, it is evident that a unifying elec-trochemical thread exists for the various parts of the mechanisticpathway. However, it is important to recognize that bioactivity ismultifaceted. In the present case, this may involve Shape, Vibrationand Electrochemistry. Usually, the difcult part is assigning relativeimportance to the contributors. However, the electrochemicalapproach appears to be more comprehensive. In relation to Elec-trochemistry, future works should determine the validity of thisapproach, particularly relative to unanswered questions. There

Table 2Dipole moments of homologous aldehydes [13].

Aldehyde Dipole moment (DM)

Acetaldehyde 2.75Propanal 2.52e2.86results provide important support for the electrochemical thesis inrelation to receptor binding by odorant and subsequent electricalactivity.

8. Comparison of vibration and electrochemical theories

Generally, odorant molecular rationalized Vibration Theory canalso be accommodated within the electrochemical framework. Anexample is the class of molecules with no dipole (see above). In thefollowing cases, odors are different. Ferrocene and nickelocenewhich have similar shapes, possess different chemical properties.Enantiomers (mirror images) of carvone contain identical func-tional groups, but different odors. Because of the difference instereochemistry, they may bind at different receptors giving rise todifferent interactions of the odorant EFs with protein EFs. Incomparison of acetophenone and its deuterated counterpart,studies have shown different chemical characteristics. In the alde-hyde homologous series, the DM values are essentially identical(Table 2). However, odors of the odds (C7, C9, C11) are waxy,whereas the evens (C8, C10, C12) are citrus. Spectroscopic studiesshow that the aldehydes rotate much more freely in the evens, butolfactory signal transduction. Reports address electrochemistry andcell signaling or signal transduction in connection with variousother items, such as, a review [71] role of proteins and secondmessenger [72], G-protein [73], scaffolding proteins [74,75],proteins and memory [76], olfactory motor gene deletion [77],cyclic nucleotide-activated channel [78], protein kinase C andadenylate cyclase [70], second messengers [79], postdocking ligandbehavior [80] and gene effect [81]. There is other pertinent litera-ture [82,83]. A particularly relevant study deals with enhancementof the cellular olfactory signal by electrical stimulation [84]. Uponodorant recognition, the electrical cellular activity is enhancedfollowing each electrical stimulus pulse. Electrical stimulation canButanal 2.72

Lincoln is acknowledged. The author is grateful to Professor

1e9.

[7] P. Kovacic, Unifying electrostatic mechanism for metal cations in receptors

lectrand cell signaling, J. Recept. Signal Transduct. 28 (2008) 153e161.[8] P. Kovacic, R. Somanathan, Unifying mechanism for metals in toxicity, carci-

nogenicity and therapeutic action: integrated approach involving electrontransfer, oxidative stress, antioxidants, cell signaling and receptors, J. Recept.Signal Transduct. 30 (2010) 51e60.

[9] P. Kovacic, Simplifying the complexity of cell signaling in medicine and the lifesciences: radicals and electrochemistry, Med. Hypothesis 74 (2009) 769e771.

[10] L. Turin, A spectroscopic mechanism for primary olfactory reception, Chem.Senses. 21 (1996) 773e791.

[11] L. Turin, The Secret of Scent. Harper Collins, New York, 2006, pp. 1e193.[12] C. Burr, The Emperor of Scent. Random House, New York, 2002, pp. 1e305.[13] D.R. Lide (Ed.), CRC Handbook of Chemistry and Physics, Ninetyth ed. CRC

Press, New York, 2009e2010, pp. 9e52 to 9-57.[14] C. Arnaud, Weak forces, Chem. Engin. News 85 (2007) 12.[15] S. Hohng, R. Zhou, M.K. Nahas, J. Yu, K. Schulten, D.M.G. Lilley, T. Ha, Fluo-

rescence-force spectroscopy maps two dimensional reaction landscape of theHolliday junction, Science 318 (2007) 279e283.

[16] K.J. Ressler, S.L. Sullivan, L.B. Buck, Information coding in the olfactory system:evidence for a stereotyped and highly organized epitope map in the olfactorybulb, Cell 79 (1994) 1245e1255.[2] P. Kovacic, R. Somanathan, Electromagnetic elds: mechanism, cell signaling,other bioprocesses, toxicity, radicals, antioxidants and benecial effects,J. Recept. Signal Transduct. 30 (2010) 214e226.

[3] P. Kovacic, Bioelectrostatics: review of widespread importance in biochem-istry, J. Electrostat. 66 (2008) 124e129.

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References

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10. Conclusion

In addition to the Shape and Vibration theories, the electro-chemical approach provides a novel perspective. The four parts ofthe theory are supported by considerable literature evidence. Thereis a unifying thread based on electrochemistry involving dipolemoments, electric elds, receptors, neurons, cerebral olfactorycortex, cell signaling and electron transfer. There appears to bea similarity to taste in electrochemical mode of action [92].

Acknowledgments

Editorial assistance by Thelma Chavez, Ashley Berry and Kirstie

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Mechanism of smell: Electrochemistry, receptors and cell signalingIntroductionA. odorant molecules and dipoles: limited correlationB. interaction of odor molecule EF with receptor EFsC. receptor-ligand dipolar interaction with olfactory neuronsElectro-olfactogramsExternal electrical stimulus

D. cerebral olfactory cortexElectron transferCell signalingComparison of vibration and electrochemical theoriesOther aspectsConclusionAcknowledgmentsReferences