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 and muscle cells.

Key Concepts

• Definition:
  • The resting membrane potential is the voltage difference between the inside and outside of a cell when it is not transmitting signals.
  • Typically ranges from -60 to -90 millivolts (mV), with the inside of the cell being negative relative to the outside.
• Ion Distribution:
  • Inside the Cell: High concentration of potassium ions (K+) and negatively charged proteins.
  • Outside the Cell: High concentration of sodium ions (Na+) and chloride ions (Cl-).
• Key Players:
  • Ion Channels: Proteins that allow specific ions to pass through the cell membrane.
  • Na+/K+ ATPase (Sodium-Potassium Pump): Maintains the concentration gradients of Na+ and K+ by pumping Na+ out of the cell and K+ into the cell using ATP.

Mechanisms Contributing to Resting Membrane Potential

• Diffusion of Ions:
  • K+ ions diffuse out of the cell through potassium channels due to the concentration gradient, making the inside more negative.
  • Na+ ions tend to diffuse into the cell, but the membrane is less permeable to Na+ compared to K+.
• Electrochemical Gradient:
  • The balance between the concentration gradient and the electrical gradient (voltage difference) determines the movement of ions.
  • For K+, the electrical gradient pulls K+ back into the cell as it diffuses out, creating a dynamic equilibrium.
• Sodium-Potassium Pump:
  • Actively transports 3 Na+ ions out of the cell and 2 K+ ions into the cell against their concentration gradients using energy from ATP.
  • Helps maintain the negative resting membrane potential by keeping the concentration of Na+ low inside the cell and K+ high inside the cell.

Nernst Equation

• The Nernst equation calculates the equilibrium potential for a specific ion based on its concentration gradient across the membrane:
• Equation: E_ion = (RT/zF) * ln([ion]_outside / [ion]_inside)
  • E_ion: Equilibrium potential for the ion.
  • R: Universal gas constant.
  • T: Temperature in Kelvin.
  • z: Charge of the ion.
  • F: Faraday's constant.
  • [ion]_outside: Concentration of the ion outside the cell.
  • [ion]_inside: Concentration of the ion inside the cell.

Goldman-Hodgkin-Katz (GHK) Equation

• The GHK equation calculates the resting membrane potential considering the permeability and concentration of multiple ions:
• Equation: V_m = (RT/F) * ln((P_K[K+]_outside + P_Na[Na+]_outside + P_Cl[Cl-]_inside) / (P_K[K+]_inside + P_Na[Na+]_inside + P_Cl[Cl-]_outside))
  • V_m: Resting membrane potential.
  • P_K, P_Na, P_Cl: Permeabilities of K+, Na+, and Cl- ions.

Clinical Relevance

• Hyperkalemia:
  • Elevated potassium levels in the blood can reduce the resting membrane potential, making cells more excitable.
  • Symptoms: Muscle weakness, arrhythmias, and cardiac arrest.
• Hypokalemia:
  • Low potassium levels in the blood can increase the resting membrane potential, making cells less excitable.
  • Symptoms: Muscle weakness, cramps, and arrhythmias.
• Drugs Affecting Ion Channels:
  • Medications that block or open ion channels can alter the resting membrane potential and affect cell excitability.
  • Examples: Local anesthetics (block Na+ channels), antiarrhythmic drugs (modify ion channel activity).

Summary

The resting membrane potential is a critical aspect of cellular function, particularly in excitable cells like neurons and muscle cells. It is established by the distribution of ions across the cell membrane and maintained by ion channels and pumps. Understanding the mechanisms behind the resting membrane potential is essential for comprehending how cells generate and transmit electrical signals, as well as for diagnosing and treating related medical conditions.

How Drugs Affect Resting Membrane Potential

Drugs can have a significant impact on the resting membrane potential and cellular excitability, particularly in excitable tissues like neurons and cardiac or muscle cells. They achieve this mainly by altering the function of ion channels or influencing the activity of ion pumps. Below are some common mechanisms by which drugs can affect the resting membrane potential:

• Sodium Channel Blockers:
  • These drugs inhibit sodium (Na+) influx by blocking sodium channels, reducing the excitability of cells.
  • Sodium is a key ion responsible for depolarization. Blocking Na+ channels makes it more difficult for the cell to reach the threshold for an action potential.
  • Examples: Local anesthetics (e.g., lidocaine) and antiarrhythmic drugs (e.g., quinidine, procainamide) reduce Na+ influx, leading to decreased excitability of neurons and cardiac cells.
• Potassium Channel Blockers:
  • Blocking potassium (K+) channels prevents K+ from leaving the cell, which prolongs depolarization and makes the resting membrane potential less negative.
  • As a result, cells remain depolarized longer, which can influence heart rhythms and neuronal firing.
  • Examples: Antiarrhythmic drugs such as amiodarone or sotalol delay repolarization by blocking K+ channels, helping control abnormal heart rhythms.
• Calcium Channel Blockers:
  • These drugs reduce the influx of calcium ions (Ca2+), which can affect the membrane potential, especially in cardiac and smooth muscle cells.
  • By limiting Ca2+ entry, they reduce cellular excitability and muscle contraction, helping to lower blood pressure and prevent abnormal heart rhythms.
  • Examples: Verapamil, diltiazem, and amlodipine are calcium channel blockers used for treating hypertension and arrhythmias.
• Sodium-Potassium Pump Inhibitors:
  • Inhibitors of the Na+/K+ ATPase pump prevent the active transport of Na+ out of and K+ into the cell, disrupting the ion concentration gradient.
  • This leads to a more depolarized resting membrane potential because the concentration of Na+ increases inside the cell, while K+ decreases inside.
  • Examples: Cardiac glycosides (e.g., digoxin) inhibit the Na+/K+ ATPase, which can increase intracellular calcium, strengthening heart contractions while also affecting membrane potential.
• Ion Channel Modulators:
  • Some drugs act as modulators, enhancing or inhibiting the function of ion channels indirectly, thus altering membrane potential and cell excitability.
  • Examples: Benzodiazepines (e.g., diazepam) modulate GABA receptors, which in turn influence chloride (Cl-) channels, causing hyperpolarization and reducing neuronal excitability.

Clinical Implications

By altering the resting membrane potential, drugs can have profound effects on the nervous system, cardiac function, and muscle contraction. Understanding how specific drugs influence ion channels and pumps is critical for managing conditions like arrhythmias, hypertension, epilepsy, and pain, as well as for anesthesia management.