Lecture 2 - neurophysiology

what is neurophysiology

the study of electrical and chemical processes in neurons

what is electrochemical signalling?

information flows within a neuron via electrical signals; information passes between neurons through chemical signals

what are the two fundamental neuronal signals?

action potentials

synaptic transmission

what is the base property of all living cells and their electrical charge

more negative on the inside than the outside

what are ions

electrically charged molecules

what are anions?

negatively charged molecules

what are cations

positively charged molecules

what are the common ions involved in the electrical signalling of neurons?

Na+

K+

Cl-

what is diffusion?

ions flow from areas of high concentration to low concentration

what is electrostatic pressure

like charges repel, opposite charges attract

what is the lipid bilayer

the cell membrane which is made of two layers of fat (lipids), separating two fluid areas

1. inside the cell (cytoplasm)

2. outside the cell (extracellular fluid)

what is the membrane potential

the electrical voltage difference across a cell’s membrane, that is created by the uneven distribution of ions inside and outside the cell, causing one side of the membrane to be more positively or negatively charged than the other

what is the formula for membrane potential?

V_m = V_in - V_out

what is the typical membrane potential

-65 mV

why is the membrane potential typically -65 mV

Because of the unequal distribution of ions and the selective permeability of the membrane — especially due to potassium leak channels that let K⁺ leave the cell, making the inside more negative

explain how resting membrane potential is established in glial cells?

K+ inside the cell = 400 mM

K+ outside the cell = 20 mM

at, rest the membrane is only permeable to K⁺, meaning that K⁺ will naturally flow out of the cell through diffusion and as K⁺ ions leave, the inside becomes more negative

when does the equilibrium potential occur

when chemical driving force = electrical driving force

what is the resting membrane potential in glial cells?

-75mv

how is the electrical gradient created?

there is more K+ inside than outside the cell → K+ diffuses out

movement of positively charged ions makes the inside more negative, creating this voltage difference

describe how a cell reaches equilibrium potential

there are two forces that act on K+ in a glial cell

1. chemical forces pushes K+ out (concentration gradient)

2. electrical force pulls K+ back in (negative charge inside)

when these two forces balance each other, membrane potential stabilize at equilibrium potential which for K+ is -75 mV in glial cells

why is the Nernst Equation significant?

tells us the exact membrane voltage at which one specific ion is at equilibrium. If the actual membrane potential is different, that ion will be pushed to move across the membrane until it reaches that balance (or gets blocked/stopped).

1. explains resting membrane potential:

2. the more permeable the membrane is to an ion, the more that ion’s equilibrium potential will influence the membrane potential

3. action potentials involve temporary changes in membrane permeability to different ions and the Nernst equation help us understand why ions move during these events

what are the major ions involved in resting membrane potential for neurons?

K+

Na+

Cl-

which of the major ions involved in resting membrane potential for neurons has permeability?

slight Na+

what is the resting membrane potential for neurons?

-65 mV

why is the resting membrane potential for neurons different than for glial cells?

some Na+ leaks in neurons causing resting potential to be slightly less negative than glial cells

what is Na+/K+ ATPase pump?

essential for maintain the resting membrane potential in neurons

Na+ naturally leaks into the neuron and K+ leaks out, eventually would erase the membrane potential

Na+/K+ pump fixes that by actively pumping ions against their natural direction by pumping out 3 Na+ and pump in 2 K+

describe the resting membrane potential in neuron with respect to CI-

there is a high concentration of Ci- outside the cell than inside

concentration gradient: more Ci- outside than inside, so gradient tries to drive Ci- inside the neuron (diffusion)

electrical gradient: inside of neuron is negatively charged and Cl- is also negative, this pushes Cl- push (electrostatic pressure)

what is the equilibrium potential of a neuron?

-70 mV

why is the equilibrium potential of a neuron what it is?

resting membrane potential is -65 mV, which is slightly less negative than Cl- equilirbium potential, so small amount of Cl- enters. Making the equilibrium potential at -70 mV

describe how the goldman’s equation is significant

1. membrane potential depends on more than just one ion (K+, Na+ , and Cl- all influence the membrane potential)

2. some ions have more impact than others due to selective permeability (at rest, membrane is more permeable to K+ than Na+, so K+ contributes more to the resting potential)

3. changing either the ion concentration or the membrane’s permeability to those ions will change the membrane potential (permeability changes rapidly during an action potential)

what is the action potential?

a brief, rapid electrical signal that travels along the membrane of a neuron (or muscle cell). It’s how neurons send messages over long distances

describe the states of the voltage-gated ion channels

1. resting

   1. VG channel closed: + charged extracellular side & - charged cytoplasmic side

2. activated

   1. VG channel open, activation gate open, inactivation gate closing

3. inactivated

   1. channel closed by inactivation gate

what is the refractory period

a phase in the action potential where the voltage-gated ion channels are inactivated and cannot fire another action potential

what is hyperpolarized and the name for it

high → low; -65 mv → -75 mv

inhibited

what is depolarized and the name of it

low → high; -65 mv → -55 mv

excited

what is a voltage gated ion channel?

a channel that allows the passing of ions through a gate that is controlled by voltage

describe how voltage-gated Na+ channels work in the action potential

resting: closed at -70 mV

activated: open between -55 mV and +40 mV

inactivated: shut again at +40 mV and -70 mV

when opened, Na+ rushes in, making the inside more positive

describe how voltage-gated K+ channels work in the action potential

open after Na+ channels to restore the resting potential

K+ flows out due to

• high internal K+

• positive charge inside

slow closing leads to hypoerpolarization

describe Ohms law and the meaning of each letter

V = I * R

V = voltage (membrane potential)

I = current (movement of ions)

R = resistence (difficulty of ions’ ability to move)

G = conductance

what happens if we hyperpolarize the cell

cell becomes more hyperpolarized dependent on the strength of the stimulus. Stimuli travel passively and gradually diminish in amplitude as they move down the axon

what happens if we depolarize the cell

A depolarizing stimulus that reaches threshold triggers an action potential. The AP continues to propagate down the axon to the second adjacent segment, maintaining its full size and shape

summarize the key characteristics of action potentials

• APs are produced by movement of Na+ ions into the cell

• at the peak of an AP, the concentration gradient pushing Na+ ions into the cell equals the positive charge driving them out

• membrane shifts briefly from a resting state to an active state and back

summarize the steps of action potentials

voltage-gated Na+ channels open in response to depolarization and Na+ ions enter

continues until membrane potential reaches Na+ equilibrium potential of +40 mV

as cell interior becomes more positive, voltage-gated K+ channels open

K+ moves out until the resting potential is restored

describe AP transmission

one way train

all or none process

what is absolute refractory period

Na+ inactivation gate and cannot elicit a 2nd AP

what is relative refractory period

some Na+ voltage gated channels have returned to rest

sufficiently strong stimulus can elicit another AP

describe the key characteristics of AP

APs are regenerated along the axon — each adjacent section is depolarized and a new action potential occurs

APs travel in one direction because of the refractory state of the membrane after a depolarization

APs are an all or none process — when threshold is reached an AP will occur at the same strength every time

how can we increase the speed of propagation of action potentials

1. reduce friction: bigger axons for faster transmission

2. add myelin sheath to increase speed by allowing AP to jump between the gaps in the myelin called nodes of ranvier

describe the importance of myelin with respect to multiple sclerosis

MS is autoimmune disease where the body’s immune system attacks the myelin sheath in the CNS. The loss of myelin slows or bocks AP conduction → wide range of neurological symptoms

what are some of the methods in increasingly indirect reflections of APs to record APs

intracellular electrophysiology

EEG

extracellular electrophysiology

calcium imaging

Functional imaging