Makindo Medical Notes

⚡ The resting membrane potential is the electrical potential difference across the cell membrane when a cell is in a non-excited state. It is essential for the function of excitable cells such as neurons, skeletal muscle, and cardiac tissue.

🔑 Key Concepts

• Definition:
  • Voltage difference between inside and outside of a cell at rest.
  • Usually -60 to -90 mV (inside more negative).
• Ion Distribution:
  • Inside: High K⁺, negatively charged proteins.
  • Outside: High Na⁺, Cl⁻.
• Key Players:
  • Ion channels → selective permeability to ions.
  • Na⁺/K⁺ ATPase → 3 Na⁺ pumped out, 2 K⁺ pumped in per ATP hydrolysed.

📊 Typical Ion Concentrations (mM)

Ion	Inside Cell	Outside Cell
Na⁺	10–15	145
K⁺	140	4
Cl⁻	4–20	110
Ca²⁺	~0.0001	1.8

⚙️ Mechanisms Establishing Resting Potential

• Diffusion of Ions:
  • K⁺ leaks out → leaves inside more negative.
  • Na⁺ leaks in slowly (membrane less permeable to Na⁺).
• Electrochemical Gradient:
  • K⁺ efflux balanced by electrical pull back in → equilibrium.
• Sodium-Potassium Pump:
  • Maintains gradients → pumps Na⁺ out, K⁺ in.
  • Contributes to negativity of membrane potential.

📐 Equations

• Nernst Equation: Calculates equilibrium potential for a single ion:
  E_ion = (RT/zF) * ln([ion]_outside / [ion]_inside)
• Goldman–Hodgkin–Katz (GHK): Combines permeabilities of K⁺, Na⁺, Cl⁻ to predict overall membrane potential:
  V_m = (RT/F) * ln((P_K[K⁺]_out + P_Na[Na⁺]_out + P_Cl[Cl⁻]_in) / (P_K[K⁺]_in + P_Na[Na⁺]_in + P_Cl[Cl⁻]_out))

🏥 Clinical Relevance

• Hyperkalaemia: ↑ K⁺ outside → resting potential less negative → cells more excitable.
  ⚠️ Symptoms: muscle weakness, arrhythmias, cardiac arrest.
• Hypokalaemia: ↓ K⁺ outside → resting potential more negative → harder to excite.
  ⚠️ Symptoms: cramps, weakness, arrhythmias.
• Drugs & Channelopathies: Alter excitability by modifying ion flux.

💊 How Drugs Affect Resting Membrane Potential

• 🔵 Sodium Channel Blockers: ↓ excitability by blocking Na⁺ influx.
  Examples: Lidocaine (local anaesthetic), Quinidine (antiarrhythmic).
• 🟢 Potassium Channel Blockers: Prolong repolarisation, keep cells depolarised longer.
  Examples: Amiodarone, Sotalol.
• 🟡 Calcium Channel Blockers: ↓ Ca²⁺ entry, ↓ contraction & excitability.
  Examples: Verapamil, Diltiazem, Amlodipine.
• 🔴 Na⁺/K⁺ ATPase Inhibitors: Disrupt gradients, depolarise cells.
  Example: Digoxin → ↑ intracellular Ca²⁺, stronger heart contraction.
• 🟣 Ion Channel Modulators: Indirectly alter excitability.
  Example: Benzodiazepines → enhance GABA → Cl⁻ influx → hyperpolarisation.

📌 Clinical Implications

Altering resting potential changes excitability of neurons, cardiac fibres, and muscle cells. This underpins treatment of arrhythmias, epilepsy, hypertension, pain, and anaesthesia.

📝 Summary

Resting potential (~ -70 mV) results from K⁺ leak, Na⁺/K⁺ pump, and ion gradients. 👉 Hyperkalaemia → excitable, hypokalaemia → less excitable. 👉 Many drugs act by modifying ion flux across membranes. Understanding these mechanisms links cell physiology directly to clinical pharmacology.