A&P Lecture 7- Nervous System Physiology

Resting membrane potential value

Approximately -70 mV, results primarily from K+ movement out of cell

Why resting potential is mainly K+

In a resting cell, all channels are closed except a subset of K+ channels (leak channels)

Two mechanisms generating membrane potential

1) Membrane ion channel selectivity, 2) Differential pumping of ions by Na+/K+ ATPase

Na+/K+ ATPase stoichiometry

Pumps 3 Na+ out and 2 K+ in, using ATP

Intracellular vs extracellular Na+

~15 mM inside, ~150 mM outside (10x higher outside)

Intracellular vs extracellular K+

~100 mM inside, 4-5 mM outside (20-25x higher inside)

Hyperpolarization definition

Membrane becomes more negative/more polarized (e.g., -70 to -80 mV)

Hyperpolarization = IPSP

Inhibitory postsynaptic potential

Depolarization definition

Membrane becomes less negative/less polarized (e.g., -70 to -60 mV)

Depolarization = EPSP

Excitatory postsynaptic potential

Increased K+ conductance effect

Hyperpolarization (IPSP) - K+ exits cell, more negative inside

Increased Cl- conductance effect

Hyperpolarization (IPSP) - Cl- enters cell, more negative inside

Increased Na+ conductance effect

Depolarization (EPSP) - Na+ enters cell, less negative inside

Increased Ca2+ conductance effect

Depolarization (EPSP) - Ca2+ enters cell, less negative inside

Summary - hyperpolarization causes

Increased outward K+ movement OR inward Cl- movement

Summary - depolarization causes

Inward Na+ or Ca2+ movement

Action potential definition

Rapid change in membrane potential where inside becomes less negative

Action potential occurs in

Only excitable cells (neurons and muscle)

Action potential results primarily from

Movement of positive ions into cell (Na+ and/or Ca2+)

Equilibrium potential definition

Membrane potential at which net migration of an ion is zero (ions entering = ions leaving)

Potassium equilibrium potential (EK)

-84 mV (5 mM K+ outside, 140 mM inside)

Chloride equilibrium potential (ECl)

-64 mV (10 mM Cl- inside, 110 mM outside)

Sodium equilibrium potential (ENa)

approximately +66 mV (~12 mM inside, 140 mM outside)

Calcium equilibrium potential (ECa)

approximately +137 mV (~70 nM inside, 2 mM outside)

Default state of most ion channels

Closed; exception is K+ leak channels which are always open

Four ion channel activation mechanisms

Voltage-gated, ligand-gated (extracellular ligand), ligand-gated (intracellular ligand), stress-activated

Order of channel opening in action potential

Na+ channels open first (depolarize), then K+ channels open (repolarize)

Insulin release mechanism - trigger

Increased glucose → increased ATP → closes K-ATP channels → depolarization → opens voltage-gated Ca2+ channels → Ca2+ entry triggers exocytosis of insulin vesicles

Mg2+ effect on membrane

Stabilizes membrane (cells less likely to depolarize) by closing certain Ca2+ channels, lowering cytoplasmic Ca2+

Mg2+ clinical effects

Decreases cardiac arrhythmias, decreases uterine contractions (prevents preterm labor), decreases neuron activity, treats constipation (milk of magnesia, keeps water in GI tract)

Soma function

Cell body; integrates synaptic signals, generates firing rhythms, links activity to gene expression

Dendrites function

Receive information/synaptic input

Axon hillock (initial segment) function

Initiation of action potential

Axon function

Transmission of action potential

Axon terminal function

Release of neurotransmitter

Synapse function

Transmits message to other cells

Dendritic spines

Sites of excitatory synaptic contact

Dendrite shafts

Sites of inhibitory synaptic contact; transmit all synaptic signals to soma

Axon signal transmission pattern

All-or-none fashion to postsynaptic follower cells

Initiation of axonal conduction (resting state)

Hyperpolarized

Initiation of axonal conduction (active state)

Depolarized

Termination of axonal conduction

Repolarization back to resting hyperpolarized state via ion pumps (ATP used)

Afferent vs efferent

Afferent = sensory input (two tracts

Peripheral nervous system divisions

Somatic and Autonomic

Autonomic nervous system dual innervation

Most organs have both parasympathetic (acetylcholine) and sympathetic (epinephrine/norepinephrine) innervation

Exceptions to dual innervation

Skin and blood vessels

Parasympathetic effects on heart/lungs

Slows heartbeat, constricts bronchi (acetylcholine)

Sympathetic effects on heart/lungs

Accelerates heartbeat, dilates bronchi (epinephrine/norepinephrine)

Enteric nervous system

Contained within GI tract; considered part of ANS because it innervates smooth muscle and glands

Pseudounipolar neurons

Sensory neurons

Bipolar neurons

Sensory neurons in special senses (vision, hearing, taste, smell, balance)

Anaxonic neurons

No defined axon; found in brain and retina

Multipolar neurons

Interneurons without long axons

Efferent neuron type

Typical multipolar neuron; most motor neurons

Anterograde transport

Movement toward axon terminal; carries mitochondria, cytoskeletal elements, neurotransmitter synthesis enzymes

Retrograde transport

Movement toward cell body; returns organelles for degradation/recycling

Glial cells - proportion

~85% of cells in nervous system

Schwann cells function (PNS)

Myelination, secrete neurotrophic factors, help repair/guide cut nerves to target muscles

Satellite cells function (PNS)

Support cell bodies

Oligodendrocytes function (CNS)

Myelination

Astrocytes function (CNS)

Blood-brain barrier, take up K+

Microglia function (CNS)

Scavengers/immune system

Ependymal cells function (CNS)

Secrete cerebrospinal fluid

Guillain-Barré syndrome

Destruction of myelin in Schwann cells (PNS)

Multiple sclerosis

Destruction of myelin in oligodendrocytes (CNS)

Temporal summation

Several stimuli received in quick succession can reach threshold and cause action potential

Spatial summation

Simultaneous stimuli at different places summing to reach threshold

Action potential ion sequence

Resting potential → depolarizing stimulus → Na+ channels open (depolarize) → Na+ channels close, K+ channels open → K+ efflux (repolarize/hyperpolarize) → return to resting

Absolute refractory period

Period during Na+ channel activity when another AP cannot be initiated

Sodium channel resting state

Activation gate closed, inactivation gate open

Sodium channel during depolarization

Activation gate open, inactivation gate open (Na+ flows in)

Sodium channel during repolarization

Activation gate closes, inactivation gate open

Local (eddy) currents role

Allow depolarization to spread to adjacent membrane regions, propagating the action potential

Why action potential propagates unidirectionally

Refractory region immediately upstream prevents backward propagation

Saltatory conduction

Myelination by Schwann cells speeds conduction velocity by jumping between nodes of Ranvier

Neurotransmitter release relationship to stimulus

Amount of neurotransmitter released is proportional to stimulus strength

Normal plasma K+ range

3.5 to 5 mM

Hypokalemia effect on membrane

Hyperpolarizes cell membrane → muscle weakness

Hyperkalemia effect on membrane

Brings membrane closer to threshold → cardiac arrhythmias

Nerve terminal channel type

Voltage-gated Ca2+ channels (not Na+) trigger neurotransmitter release via exocytosis

Acetylcholine synthesis

Choline + Acetyl CoA → Acetylcholine (via enzyme), stored in synaptic vesicles

Acetylcholine inactivation

Acetylcholinesterase (AChE) breaks down ACh into choline + acetate

Alzheimer's disease neurotransmitter link

Too little acetylcholine in CNS (memory loss)

Alzheimer's treatment

Donepezil (Aricept) - inhibits cholinesterase, raises ACh levels

Parkinson's disease

Low dopamine

Schizophrenia

High dopamine

Depression

Low serotonin

Receptor types for neurotransmitters

Ion channels (fast-acting, ligand-gated) or G protein-coupled receptors (slower-acting, second messengers)

Glutamate AMPA receptor effect

Net Na+ entry depolarizes postsynaptic cell

Glutamate NMDA receptor mechanism

Depolarization ejects Mg2+ block, opens channel, allows Ca2+ entry, activating second messenger pathways

Synapse "cleaning" mechanisms

Enzymes, transporters, blood flow, and glial cells remove neurotransmitter from synapse