Physio 3: Electrophysiology

What is diffusion?

initial driving force for the movement of molecules

How do molecules move in diffusion

high to a low concentration (down the gradient)

What types of equilibrium (or disequilibrium) exist in body cells?

Cells of the body are:

In chemical disequilibrium

In osmotic equilibrium

In electrical disequilibrium

Cells in chemical disequilibrium

More Na+ and Cl- outside, more K+ and negatively charged proteins inside.

Cells in osmotic equilibrium

water moves freely across the membranes until osmotic pressure is equalized (290 mosm inside and outside)

Cells in electrical disequilibrium

few extra negative ions inside cells and their matching positive ions are outside

Electrochemical equilibrium

electrical gradient exactly offsets the concentration gradient.

How is electrochemical equilibrium calculated

Nernst equation

Nernst equation

determines the equilibrium (reversal) potential for a specific ion based on its charge and concentration difference across the membrane

Nernst potential (reversal)

know the numbers

What is membrane potential

Electrical potential difference across a cell membrane. Caused by uneven distribution of ions across a cell membrane.

What ions does membrane potential determine the potential difference for?

ALL ions across the membrane

What factors determine membrane potential?

- concentration of ions in ECF and ICF

- polarity of each ion (+/-)

- permeability of the membrane to the ions

Overall cell charge distribution

+ charges line up on the surface establishing a polarity of a "net negative" internal environment

Goldman-Hodgkin-Katz Equation

predicts membrane potential that results from the contribution of all ions that can cross the membrane (similar to nernst but w/ permeability factored in)

If the permeability of ion = 0, how much do they contribute to the membrane potential

they do not contribute

Permeability = 1, how much does it contribute to the membrane potential

100% permeable

Resting membrane potential table

know the numbers

Resting membrane potential of neurons

-60 to -70 mV

Resting potential of skeletal muscle cells

-85 to -95 mV

Resting membrane potential of cardiac muscle cell

-80 to -90 mV

Reversal potential of potassium

- 88 (~ -90mV)

Reversal potential of sodium

+60 mV

Reversal potential of Ca2+

123 mV

Reversal potential of Cl-

-47 mV

What factors contribute to the resting membrane potential

- Na+/K+-ATPase establishing Na and K gradient

- K+ leak channels letting K+ exit, leaving behind (-) charge

- Minor contribution for Na+ influx and the Na+/K+ pump, which adds about -4 mV

Na concentration inside/outside the cell

14/142 = 0.1 (factor of 10)

K concentration inside/outside the cell

140/4 = 35 (3x10 driving force stronger inside)

How can we record membrane potentials

with a silver-silver chloride electrode

4 main states of an action potential

- resting phase

- depolarization

- repolarization

- hyperpolarization (after potential)

resting potential of a neuron is at

-70mV

threshold potential

The minimum membrane potential that must be reached in order for an action potential to be generated = -55 mV

Role of Na+ in neuronal action potential

drives rapid depolarization (in the positive direction)

Depolarization occurs due to the opening of which channel

Na+ voltage gated channels

Repolarization occurs due to the opening of

K+ voltage channels open back to rest

hyperpolarization phase

membrane potential temporarily becomes more negative than resting membrane potential

In which phase of action potential is the membrane said to be polarized

resting phase (-70 mV)

Overshoot of nerve fibers in action potential

membrane potential reaches + 35 mV

Na channels contain how many gates

two

K channels contain how many gates

one

Resting state Na+ channels (before stimulation)

activation gate closed, inactivation gate open --> channel ready but inactive (-70 mv)

Depolarization rising phase in Na+ channels

membrane potential reaches the threshold (-70 to + 35 mV)

Both gates open --> Na+ rushes into the cell, causing depolarization

Peak/overshoot phase in sodium ion channels

inactivated (+35 to -70 mV, delayed), activation gate open, inactivation gates close (delayed) --> Na+ flow stops

Repolarization phase - Na+ channels

Resting (-70 mV) activation gate closed, inactivation gate open (channel inactive)

Resting state K+ channels

(-70mV), gate is closed at rest

Activation of K+ channels

Slow activation (+35 to -70mV) during depolarization and fully opens in repolarization causing potassium to leave the cell making the inside more negative

Hyperpolarization of potassium channels

K+ channels slow to close --> cause membrane to become more negative (afterpotential) before returning to -70mV

Na+ channel inactivation gates ------ as the channel approaches -70 mV

rapidly reopen

Na+ channel activation gates will be rapidly closed at ------

- 70 mV

Describe the concept of threshold

when depolarization reaches -55 mV, voltage gated Na+ channels open, generating an all or nothing action potential. If threshold isn't reaches no action potential fires

Positive afterpotential tail phase

K⁺ channels remain open longer than needed, allowing excess K⁺ to leave the cell. This drives the membrane potential to undershoot below its resting value (-80 mV to -90 mV) before it returns to -70 mV

Absolute refractory period

no second action potential can be triggered during this point. Na+ channels are inactivated

Relative refractory

Some Na+ channels reset, a second action potential may be triggered but it must be coupled with an additional larger stimulus.

Structure of an axon

axon hillock, axon fiber, axon terminal, and myelin sheaths

Myelin sheaths

insulate axons, preventing current leak and enabling saltatory conduction

Saltatory conduction

- the action potential propagation along myelinated axons between Nodes of Ranvier, speeding transmission of action potential.

What forms the myelin sheath

Schwann cells

Absent or mutated Schwann cells can cause (clinical correlate)

Multiple sclerosis (MS) --> the action potential would move slowly and occasionally fail to continue

Plateaus mainly seen in

ventricular cardiomyocyte action potential

What causes the plateau phase of cardiac action potential?

result from a balance between Ca2+ influx and K+ efflux -> this maintains the membrane potential near 0 mV for a prolonged period, allowing sustained contraction

What is the physiological importance of the plateau

prolongs depolarization, extends the refractory period, and ensures sufficient Ca2+ entry for cardiac muscle contraction, stops summation

Neurons (nerve cells) contain

dendrites, soma, axon, terminal bouton

Chemical synapses

neurotransmitters released from presynaptic cells bind to receptors on postsynaptic membrane, most prevalent in the CNS (UNIDIRECTIONAL)

Electrical synapses

Use gap junctions for direct ion flow (between pre and postsynaptic cells) very rapid and BIDIRECTIONAL

Identify the major steps in synaptic signal transduction

1. Action potential arrives at axon terminal

2. Voltage gated Ca2+ channels open

3. Ca2+ triggers vesicle fusion via v-snare and t-snare

4. Neurotransmitter released into synaptic cleft

5. Neurotransmitter binds to postsynaptic receptors, generating EPSPs or IPSPs

6. Signal terminated by degradation, reuptake, or diffusion.

What do neurotransmitters generate when they bind to postsynaptic receptors?

EPSPs or IPSPs

How is the synaptic signal terminated?

degradation, reuptake, or diffusion

What is a neurotransmitter

messenger of neurologic information from one cell to another

Small molecule transmitters (fast or slow, where are they synthesized and absorbed)

- Rapid acting

- Mostly synthesized in the cytosol of presynaptic terminal and absorbed via active transport into vesicles

Examples of small molecule transmitters

- acetylcholine

- amines; dopamine, norepinephrine, epinephrine, serotonin, histamine

- amino acids; glutamate, GABA, Glycine, Aspartate

- nitric oxide

Neuropeptides (fast or slow, cause and effect)

- Slow synthesis but more potent and prolonged effect than small mol.

- Causes prolonged closure of Ca2+ channels, txn changes and effect may last days - years

Neuropeptides classes

- Hypothalamic releasing hormones

- Pituitary peptides

- Peptides that act on gut and brain

Where are neurotransmitters synthesized and transported?

ER and transported to the golgi for packaging into secretory granules

Co-release of neurotransmitters

co-localized in the same synaptic vesicles and released together

Co-transmission of neurotransmitters

localized in different vesicles and may be differentially regulated because of different calcium ion sensitivities or because they are located in different boutons

V-SNARE made up of

structural protein

- synaptotagmin

- synaptobrevin

T-SNARE made up of

- Syntaxin

- SNAP-25

Binding of v-snare and t-snare requires

Calcium

Acetylcholine is made from

choline and acetyl CoA

Acetylcholine binds to

cholinergic receptors in the synapse

In the synapse, ACh is rapidly broken down by the enzyme ____

acetylcholinesterase (AChE) and transported back into the axon terminal to make more Ach

Glutamate is an ______ neurotransmitter

excitatory

where is glutamate found

Widely distributed in the CNS

Glutamate binds glutamate receptors on postsynaptic membrane causing opening of which channels

Na+ and Ca2+ signals next cell to have an action potential

Glycine neurotransmitter

major inhibitory neurotransmitter in spinal cord and brainstem

Glycine binds to glycine receptors on the postsynaptic cell causing opening of which channel

Cl- channel which signals next cell to NOT have an action potential

Biogenic amines

dopamine, norepinephrine, epinephrine (Think Do Not Escape)

Which enzymes degrade dopamine, norepinephrine, and epinephrine?

MAO (monoamine oxidase) and COMT

Ionotropic receptors

Ligand-gated ion channels--fast response (NT: Ach, glutamate, glycine)

Metabotropic receptors

receptors that are associated with signal proteins and G proteins-- slower, longer-lasting effects

Example of ionotropic receptor

Nicotinic ACh receptor

Example of metabotropic receptor

Muscarinic ACh receptor

Excitatory postsynaptic potential (EPSP)

depolarizing, increases the likelihood of action potential firing (Ach, glutamate)

Inhibitory postsynpatic potential (IPSP)

hyperpolarizing, decreases the likelihood (GABA, glycine)

Neuronal summation

Neurons integrate all excitatory and inhibitory inputs in the soma. If the net depolarization at the axon hillock reaches threshold, an action potential fires.

Temporal summation

One or more presynaptic neurons transmit impulses in rapid-fire order. (if enough EPSPs occur close together, they can reach threshold and trigger action potential)

Spatial summation

think multiple presynaptic neurons firing at the same time, each at a different location on the dendrites --> can add up in space and reach threshold (fire action potential)

What is the excitatory state

Excitation is greater than inhibition --> causes neurons to fire repeatedly as long as that state is maintained.