Physiology – Membrane Potentials and Action potentials

00:00:26- ICF and ECF composition

Chief Cation Chief Anion

ECF Sodium Chloride
ICF Potassium [hosphate
All of this is due to selective membrane permeability

00:02:41- Resting membrane potential

 Permeability coefficient
 K+ > Cl- > Na+
 Potassium is the only ion permeable at rest due to leaky channels
Molecular weight Size of hydration
Sodium 23 0.18
Potassium 39 0.12
Due to hydrated size being larger, sodium is less permeable
 The resting membrane potential is always negative due to non-permeable protein anions
 Since potassium is lower outside (ECF), the concentration gradient favor potassium
moving outside
 But the negative charge inside favors pulling potassium inward due to electrical gradient
 The balance between these two is membrane potential or net flux is zero
00:07:49- Nernst potential
 Na + = +61 mv to + 65 mv
 K+ = -90mv to -94 mv
 Ca ++ = +132 mv
 Cl - = -70 mv to -65 mv
 Sodium potassium pump: two potassium in, three sodium out. Causes relative negativity,
restores membrane potential.
 Also called diffusion potential, there is equilibrium between electrical and concentration
gradient of each ion.
RT
 E= ∈Conc ( i ) /conc ( o)
Zf
 R is gas constant
 T is absolute temperature
 Z is ion valency
 F is faraday number
 Simplified as E = 61.5log[conc(in)/conc(out)]
00:15:00- Goldman Hodgkin katz equation

 Membrane potential is concept of not just one ion but three main ions.
 The membrane potential also depends:
o Permeability of ions
o Concentration of ions
o Relative importance of each ion
 E = Pna+ x Ci + PK+ x Ki + PCl- x Co / Pna+ x Co + PK+ x Ko + PCl- x Ci
 Final value is -86mV of which -4mV is from sodium potassium ATPase pump

00:21:29- Gibbs Donnan Effect

  The Donnan effect on the distribution of ions has three effect in the body introduced here
and discussed below
 First, because of charged protein (Prot-) in cells, there are more osmotically active
particulars in cell than in interstitial or intracellular fluid, and because animal cell have
flexible walls, osmosis would make them swell and eventually rupture if it were not for
the sodium-potassium adenosine triphosphate (Na, K ATPase) pumping ions back out of
cells
 Thus, normal cell volume and pressure largely depend on Na, K ATPase, also known as
the Na+ /K+ pump
 At equilibrium, there is asymmetric distribution of ions

00:27:00 – Important points related to potassium

 Most diffusible at rest
 Max leakiness
 Contributes max to RMP
 It’s equilibrium potential is almost RMP

00:28:00 – Important points related to sodium

 No role in RMP
 Main in depolarization
 Very needed for cotransports and counter transports
 Maintains osmolarity of ECF

Membrane potentials of some tissues

 Skeletal Muscles: -90mV
 Cardiac Muscles: -90mV
  Smooth muscles: -60 to -40mV
 SA node: -65 to – 55mV
 RBC: -10mV
 Neuron: -70mV

00:29:40- Action potential

 Constant amplitude
 Threshold stimulus
 Sustained effect that is propagated
 Threshold stimulus:
 Depolarization: causes by sodium channel opening, fast to open and fast to close.
Positive feedback cycle starts where one open channel opens many more. This
occurs till +35mV
 
 Repolarization: Stops fast sodium gate, reduce flux of sodium and increase
potassium conductance
 Afterhyperpolarization: maintained by sodium potassium pump

00:45:32 - Effect of ions on Action potential

 Sodium
o No role in RMP
o Increase in ECF sodium, higher size of action potential
 Calcium
o Increase in membrane excitability as calcium ions guard sodium channels
 Potassium
o Increase ECF: No concentration gradient. Threshold for excitability reduces,
easily excitable
o Decrease ECF: Very high concentration gradient, so more hyperpolarized inside.
Harder to excite now.

00:50:54- Action potential/ Graded potential

 Action potentials can be elicited only by threshold or suprathreshold stimuli and never by
subthreshold, are self-propagator and non-decremental and always depolarizing and
always depolarizing for long distance.
o Except photoceptors are hyperpolarization and cause negative potentials.
 Graded potentials are subthreshold non self propagating depolarizing or hyperpolarizing
stimuli that act on local systems.
o Receptor potentials

00:55:47- Refractory Period

 Absolute Refractory Period corresponds to the period from the time the firing level is
reached until repolarized is about one-third complete
  Relative Refractory Period corresponds from one-third of repolarization upto the end of
hyperpolarization

Ionic basis of refractory period

Concept of gate:
  Sodium gates have two gates.
 Activation gate and inactivation gate
 At -90mV when action potential occurs, activation gate opens causing rapid sodium
influx
 They open till potential is +35mV when the inactivation gate closes, while the activation
gate remains open. This causes the absolute refractory period. No threshold can now open
the gate.

Factors affecting Conduction velocity

 Larger axon diameter has less axonal resistance & allows easier passage to
axoplasmic current
 Strong electronic conduction occurs when the axoplasmic resistance is low (Ri),
membrane resistance is high (Rm) and membrane capacitance is low (Cm)
 Increase in diameter decreases the axoplasmic resistance

01:04:10- Accommodation
 When subthreshold stimulus are given in sequential patterns, the issues get adapted to it.


Square pulse, Gives AP

Weak saw tooth, No AP

01:06:31- Strength duration curve

 Rheobase: minimum strength of stimulus in producing an AP
 1mv no AP
 2mV no AP
 3mV AP starts (Rheobase)
 4mV AP

 3mV for 1ms no AP

 3mV for 2ms no AP
 3mV for 3s AP (utilization time)
 6mV for 1ms no AP
 6mV for 2ms AP (2 times AP for least time that causes AP – Chronaxie)
 Most excitable: neorun> skeletal muscle> myocardium>smooth muscle
01:10:48- Conduction velocity

 Myelinated neurons have nodes of Ranvier, only in these places there is AP. This is
called saltatory conduction.
 Non-myelinated have multiple local circuits and depolarized everywhere.
Factors affecting conducting velocity:
 Affects time and length constant
o Time constant: time required to cover 67% of the length
o Distance constant: the length that can be travelled before stopping of AP
 Larger axon diameter has less axonal resistance and allows easier passage to axoplasmic
current
 Strong electronic conduction occurs when the axonal resistance is low (Ri), membrane
resistance is high (Rm) and membrane capacitance is low (Cm)
 Increase in myelination increases the membrane resistance and decrease the membrane
capacitance
 Increase in diameter decreases the axoplasmic resistance

01:16:39- Action potential duration

Action Potential duration:

 Neuron - 1 to 3 ms
  Sk.Mus - 2 to 4 ms
 Myocardium - 200 to 400 ms
 Smooth muscle - 10 to 50 ms

01:17:10 - Clinical vignettes

1. A 39-year-old woman presents with paresthesia of the left hand that resolves 48 hours
later. History reveals an episode of weakness in the left leg 6 months prior that lasted
for 2-3 days and double vision on several occasion over the past year that lasted for
24 hours. Magnetic resonance imaging (MRI) of the brain and spinal cord reveals
lesions that are consistent with a diagnosis of multiple sclerosis. Which of the
following is expected in the patient?
(A) Increased axon diameter
(B) Increased membrane capacitance
(C) Increased membrane resistance
(D) Decreased number of axonal ion channels
Ans B
2. At the node of Ranvier, voltage gated sodium channels are inactivated and potassium
channels are activated, the membrane potentials is 10mV and falling. What phase of
the neuronal action potential is occurring?
(A) Depolarisation
(B) Overshoot
(C) Repolarisation
(D) Resting potential
Ans.C