Ions in Your Ions in Your LifeLife

An exploration into the role An exploration into the role ions play in your nervous ions play in your nervous system and what can affect system and what can affect them. them.

Your Nervous System Your Nervous System

Controls various organs of the Controls various organs of the body directly. The brain body directly. The brain also receives information also receives information from many organs of the from many organs of the body and adjusts signals to body and adjusts signals to these organs to maintain these organs to maintain proper functioning. proper functioning.

Central Nervous SystemCentral Nervous System– BrainBrain– Spinal CordSpinal Cord

Peripheral Nervous SystemPeripheral Nervous System– Autonomic SystemAutonomic System

NeuronsNeurons– Somatic System Somatic System

NeuronsNeurons

Brain Brain

Cerebral Cortex Cerebral Cortex (Thought, Language, Reasoning, Perception, (Thought, Language, Reasoning, Perception, Voluntary Movement)Voluntary Movement)

Corpus Callosum Corpus Callosum (Processes information between the (Processes information between the two sides)two sides)

MidbrainMidbrain (Vision, Hearing, Eye Movement, Body Movement) (Vision, Hearing, Eye Movement, Body Movement)

Cerebellum Cerebellum (Movement, Balance, Posture)(Movement, Balance, Posture)

Thalamus Thalamus (Sensory Processing and Movement)(Sensory Processing and Movement)

Brain Stem Brain Stem (Breathing, Heart Rate, Blood Pressure)(Breathing, Heart Rate, Blood Pressure)

Hypothalamus Hypothalamus (Body Temperature, Emotions, Hunger, Thirst)(Body Temperature, Emotions, Hunger, Thirst)

Limbic System Limbic System (Emotions)(Emotions)

Hippocampus Hippocampus (Learning and Memory)(Learning and Memory)

Spinal CordSpinal Cord A cylinder of nerve tissue extending from the A cylinder of nerve tissue extending from the

brain stembrain stem Receives sensory information and sends output Receives sensory information and sends output

motor signalsmotor signals The gray matter of the spinal cord consists The gray matter of the spinal cord consists

mostly of cell bodies and dendrites. The mostly of cell bodies and dendrites. The surrounding white matter is made up of bundles surrounding white matter is made up of bundles of interneuronal axons (tracts). of interneuronal axons (tracts).

Some tracts are ascending (carrying messages to Some tracts are ascending (carrying messages to the brain), others are descending (carrying the brain), others are descending (carrying messages from the brain). messages from the brain).

The spinal cord is also involved in The spinal cord is also involved in reflexesreflexes that do that do not immediately involve the brain.not immediately involve the brain.

Nerve cell collections extending from the base of Nerve cell collections extending from the base of the brain to just below the last rib vertebrae. the brain to just below the last rib vertebrae.

NeuronsNeurons

Three Modes of Nervous Three Modes of Nervous SignalingSignaling(Bertil Hille, 2003)(Bertil Hille, 2003)

Electrical to Electrical- Down Electrical to Electrical- Down axonaxon

Electrical to Electrical to Chemical to Chemical to Electrical- Across Electrical- Across synapse synapse Chemical to Multiple Chemical to Multiple

Electrical– Hormones Electrical– Hormones showering many cellsshowering many cells

Electrical to ElectricalElectrical to Electrical

Moving ions make electrical signals in Moving ions make electrical signals in neurons (Hodgkin & Huxley 1952)neurons (Hodgkin & Huxley 1952)

Neurons have semi permeable Neurons have semi permeable membranes (cell membranes) that allow membranes (cell membranes) that allow some ions through necessary for some ions through necessary for functions inside and not others. functions inside and not others.

Many substances in our body which are Many substances in our body which are ionically bonded, are broken into ions by ionically bonded, are broken into ions by the water found in our body. For the water found in our body. For example: NaCl breaks into the Naexample: NaCl breaks into the Na++ and and ClCl--..

Na+ Cl–

Cl– Cl–

Cl–

Na+

Na+

Na+

Faraday (1834) recognizes ions by current flowbetween charged electrodes

Salts dissociate in water to charged anions and cations. Cations have positive charge and move to the negative electrode. Franklin (1751) defines the direction of electric current as the direction of flow of positive charge. Anions move the other way.

FaradayFaraday

+ –

–+battery

current

anioncation

K+ flow

K+Cl–

Cl–

Cl–

Cl–K+

K+

Nernst (1888) describes equilibrium potentials

Suppose the membrane is permeable only to K+ ions. How does K+ move? What happens to charge? What do the other ions do?

["Permeable" means that K+ can cross the membrane by diffusion.]

NernstNernst

voltmeter = 0

K+

K+

K+

K+

K+

K+K+

K+

K+

Cl–

Cl–

Cl–Cl–

Cl–

Cl–

Cl–

Cl–

K+

– +

+–

voltmeter = EK

K+

Cl–

Cl–

Cl–

Cl–K+

K+

K+

K+

K+

K+

K+

K+K+

K+

K+

Cl–

Cl–

Cl–Cl–Cl– Cl–

Cl–

Cl–

K+

K+Cl–

IN OUT

first instant at equilibrium

K+ flow

Types of Transport ProteinsTypes of Transport Proteins

Channels CarriersATPasePumps

Mechanisms of transport across cell membranes

Ion Channel in a Ion Channel in a NeuronNeuron

Ions pass through a gated aqueous pore, which is narrow at the selectivity filter.

The voltage sensors are collections of charged residues that are dragged towards the inside of the outside as the membrane’s charge changes. They regulate gating.

Flow of ions to make Flow of ions to make signalssignals Step 1: A few NaStep 1: A few Na++ ions enter cell so cell ions enter cell so cell

inside goes positive. inside goes positive.

Step 2: A few KStep 2: A few K++ ions leave cell so cell ions leave cell so cell inside returns to rest. inside returns to rest.

Other ions that are Other ions that are

involved include involved include

ClCl-- and Ca and Ca++

Na+

K+

Problems with this flow of Problems with this flow of ionsions

Limited ions in system due to high activity Limited ions in system due to high activity or low consumptionor low consumption

Limited water in system to break down ionic Limited water in system to break down ionic bonds into ions due to high activity or low bonds into ions due to high activity or low consumptionconsumption

Local anesthetics plug NaLocal anesthetics plug Na++ channels channels – No/limited excitation, no/limited pain, no/limited No/limited excitation, no/limited pain, no/limited

movementmovement If NaIf Na++ channels open too much or K channels open too much or K++

channels open too little…channels open too little…– Too much excitation occurs leading to pain Too much excitation occurs leading to pain

epilepsy, arrhythmias, contractionsepilepsy, arrhythmias, contractions

Electrical to Electrical- Electrical to Electrical- Down AxonDown Axon

Electrical to Chemical to Electrical to Chemical to Electrical – Across Electrical – Across SynapseSynapse

Electrical impulse created Electrical impulse created by flow of ions in and out cell by flow of ions in and out cell down the axon (Cadown the axon (Ca++) triggers ) triggers the release of synaptic the release of synaptic vesicles filled with vesicles filled with neurotransmitters into neurotransmitters into synaptic gap/cleft. synaptic gap/cleft.

Neurotransmitters bind with Neurotransmitters bind with specific channels on next specific channels on next neuron to start electrical neuron to start electrical impulse (flow of ions) down impulse (flow of ions) down next neuron’s axon. next neuron’s axon.

Many neurotransmitters Many neurotransmitters each that bind to different each that bind to different sites to send different sites to send different signals to various locations signals to various locations to make our body function. to make our body function.

Once neurotransmitters are Once neurotransmitters are used they go through used they go through reuptake channels in original reuptake channels in original neuron to be reused. neuron to be reused.

Movie

NeurotransmittersNeurotransmitters

50 neurotransmitters have been 50 neurotransmitters have been discovereddiscovered

The five most common are:The five most common are:– Serotonin Serotonin (emotional stability, calming effect, sleep (emotional stability, calming effect, sleep

control, sensory perception)control, sensory perception)

– Dopamine Dopamine (pleasure, reward, euphoria)(pleasure, reward, euphoria)

– Acetylcholine Acetylcholine (memory and learning, mood and (memory and learning, mood and arousal, muscle contractions)arousal, muscle contractions)

– GABA GABA (muscle relaxant, reduces anxiety, principle inhibitor)(muscle relaxant, reduces anxiety, principle inhibitor)

– Enkephalin Enkephalin (pain suppressant)(pain suppressant)

Problems with transfer Problems with transfer of neurotransmittersof neurotransmitters Neurotransmitters get blocked from Neurotransmitters get blocked from

binding with receptors to continue signal binding with receptors to continue signal and signal is stopped. and signal is stopped.

Other molecules with similar shapes bind Other molecules with similar shapes bind to receptors and prevent to receptors and prevent neurotransmitters from being used. neurotransmitters from being used. Excitation and extra excitation occurs and Excitation and extra excitation occurs and neurotransmitter stops being produced by neurotransmitter stops being produced by the body itself. the body itself.

Neurotransmitters are blocked from going Neurotransmitters are blocked from going through reuptake transporters by original through reuptake transporters by original neuron. Extra excitation occurs and body neuron. Extra excitation occurs and body stops producing neurotransmitter. stops producing neurotransmitter.

For Example:For Example:One such neurotransmitter is called "dopamine." In the normal communication process, dopamine is released by a neuron into the synapse (the small gap between neurons). The dopamine then binds with specialized proteins called "dopamine receptors" on the neighboring neuron thereby sending a signal to that neuron.

After the signal is sent to the neighboring neuron, dopamine is transported back to the neuron from which it was released by another specialized protein, the "dopamine transporter“.

Drugs of abuse are able to interfere with this normal communication process in the brain. Cocaine, for example, blocks the removal of dopamine from the synapse by binding to the dopamine transporters. As shown in this picture, this results in a buildup of dopamine in the synapse. In turn, this causes a continuous stimulation of receiving neurons, probably responsible for the euphoria reported by cocaine abusers.

Movie

The Nervous The Nervous System gets System gets remodeled!!!remodeled!!!

Things that cause these Things that cause these problemsproblems Chemical ImbalancesChemical Imbalances AlcoholAlcohol MarijuanaMarijuana CocaineCocaine OpiatesOpiates NicotineNicotine AmphetaminesAmphetamines

Acknowledgements:Acknowledgements:

Professor Physiology and Professor Physiology and Biophysics Bertil Hille of the Biophysics Bertil Hille of the University of Washington School University of Washington School of Medicine. of Medicine.

Professor W. N. Zagotta of the University of Washington