Assertion: RMP depends on proteins and phosphate ions. Reason: Diffusion potential can be calculated using nernst equation. Choose the best statement regarding the assertion and reason.

Both true, Reason is not the explanation of assertion

Both true, Reason is the explanation of assertion

Sequence the events in neuromuscular action potential conduction: 1. Sodium channels open in the end plate 2. Calcium enters at the nerve terminal 3. Release of acetylcholine

$2 \rightarrow 3 \rightarrow 1$

$1 \rightarrow 2 \rightarrow 3$

$1 \rightarrow 3 \rightarrow 2$

$3 \rightarrow 2 \rightarrow 1$

Which of the following statements about the Na-K pump is false?

It is located on the apical membrane of cell

It is not directly involved in the generation of action potentials.

It needs ATP for its functioning

Absolute refractoriness of a neuron is due to?

Hyperpolarization of Cl channels

Opening of rectifier K+ channels

Closure of activated Na channels

Which of these is true about the highlighted transporter?

One molecule goes in, other molecule goes out

One molecule goes in and two exit

In multiple sclerosis, slow conduction of motor and sensory pathways is due to?

Dysfunction of calcium channels

A research team is developing a gene therapy approach using CRISPR-Cas9 to correct a point mutation causing sickle cell disease. They must decide between two strategies: (A) correcting the mutation in hematopoietic stem cells ex vivo, or (B) in vivo correction in bone marrow. Considering molecular physiology principles, what is the most significant advantage of strategy A over strategy B?

Strategy A allows for screening and selection of successfully edited cells before transplantation, minimizing off-target effects

Strategy A requires lower doses of viral vectors

Strategy A produces faster clinical improvement

Strategy A is less expensive to implement

Molecular Basis of Excitability for INI-CET: High-Yield Physiology Lessons

Resting Membrane Potential - Cell's Electric Bill

Electrical potential difference across a cell membrane at rest; interior negative.
Typical range: -70mV to -90mV (neurons, muscle).
Key Factors:
- K+ Dominance: High K+ permeability via K+ leak channels; K+ efflux is primary driver making inside negative.
- Ion Gradients: Maintained by Na+/K+ ATPase. High [K+] inside; high [Na+], [Cl-] outside.
- Na+/K+ ATPase: 📌 '3 Na Out, 2 K In'. Actively maintains gradients; electrogenic (contributes ~-4mV to RMP).
- Fixed Anions: Impermeable intracellular proteins (A-) contribute to negative charge.
Nernst Potential: Calculates equilibrium potential for a single ion: $E_{ion} = (61.5/z) \log([ion]{out}/[ion]{in})$ (mV at 37°C).
Goldman-Hodgkin-Katz (GHK) Equation: Calculates RMP considering relative permeabilities of multiple key ions (K+, Na+, Cl-).

⭐ The Na+/K+ ATPase pump is vital, consuming significant ATP to sustain the ionic gradients essential for RMP and thus, cellular excitability. Its electrogenic nature directly contributes a small but significant portion to the membrane negativity (approx. -4mV).

Action Potential - Nerve's Firing Squad

Rapid, transient, all-or-none electrical impulse in excitable cells (neurons, muscle).

Phases & Ion Movements:
- Resting State: Membrane at RMP (approx. -70mV).
- Threshold: Stimulus depolarizes to threshold potential (approx. -55mV).
- Depolarization: Voltage-gated $Na^+$ channels open → rapid $Na^+$ influx. Membrane potential (MP) rises to approx. +30mV.
- Repolarization: Voltage-gated $Na^+$ channels inactivate. Voltage-gated $K^+$ channels open → $K^+$ efflux. MP falls.
- Hyperpolarization: $K^+$ channels close slowly → MP briefly more negative than RMP (e.g., -80mV). $Na^+$/$K^+$ pump restores RMP. 📌 INflux of $Na^+$ causes INitiation (depolarization); Efflux of $K^+$ causes Ending (repolarization).
Key Properties:
- All-or-None Law: Fires completely if threshold is reached, or not at all.
- Refractory Periods:
  - Absolute: No new AP possible ($Na^+$ channels inactivated).
  - Relative: New AP only with stronger stimulus (some $K^+$ channels still open, MP further from threshold).

Action potential phases, ion channels, and ion flow

⭐ The 'all-or-none' principle states that an action potential either fires completely if the stimulus reaches threshold, or it doesn't fire at all. This ensures fidelity of nerve signals over distances.

Ion Channels & Propagation - Speedy Signals

Ion Channels: Membrane proteins forming selective ion pores; fundamental for neuronal excitability.

Channel Type	Activation	Key Function(s)	Example Blocker(s)
Voltage-gated Na+	Depolarization	AP upstroke (rapid influx); fast inactivation	TTX, Lidocaine
Voltage-gated K+	Depolarization	AP repolarization (efflux); slower kinetics	TEA, 4-AP
Voltage-gated Ca2+	Depolarization	Neurotransmitter release; muscle cell excitation	Verapamil, Cd2+
Ligand-gated	Ligand binding	Synaptic potentials (EPSP/IPSP); e.g., nAChR	Curare, Bicuculline

Action Potential (AP) Propagation:
- Unmyelinated Axons: Continuous conduction. Slower; AP regenerates at each point along the axon. High energy cost.
- Myelinated Axons: Saltatory conduction. Faster; AP "jumps" between Nodes of Ranvier (high Na+ channel density). Myelin insulates, ↓ion leakage, ↑speed, conserves energy.
- Speed Factors: ↑Axon diameter (↓resistance), Myelination (insulation).
Refractory Periods: Control AP frequency & direction.
- Absolute: Na+ channels inactivated. No AP possible, ensures unidirectional propagation.
- Relative: Stronger stimulus needed for AP. Some Na+ channels recovered; K+ channels still open.

⭐ Tetrodotoxin (TTX), from pufferfish, potently blocks voltage-gated Na+ channels, preventing action potential generation and causing flaccid paralysis. This highlights channel specificity.

Saltatory vs. Continuous Conduction

High‑Yield Points - ⚡ Biggest Takeaways

Resting Membrane Potential (RMP): Primarily due to high K+ permeability (K+ leak channels); Na+/K+ ATPase maintains ionic gradients.

Action Potential (AP): Reaching threshold potential triggers rapid Na+ influx (depolarization) & K+ efflux (repolarization) via voltage-gated channels.

All-or-None Law: APs fire completely if threshold is met, or not at all.

Refractory Periods: Absolute (no new AP, Na+ channels inactive) & Relative (stronger stimulus for AP) limit firing frequency.

Channelopathies: Genetic or acquired disorders of ion channels causing diseases like myotonias or arrhythmias.

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