resting membrane potential
Summary
Resting membrane potential (RMP) is the electrical charge difference across a cell membrane at rest, typically around -70 mV in neurons and -90 mV in cardiac/skeletal muscle. It is primarily determined by K+ efflux through leak channels, since the resting membrane is much more permeable to K+ than Na+. Maintained by the Na+/K+ ATPase, which sustains the ionic gradients that generate the RMP.
Detail
The resting membrane potential arises from the unequal distribution of ions (mainly Na+, K+, Cl-, and impermeant intracellular anions like proteins) across the semipermeable plasma membrane, combined with differential membrane permeability. At rest, membrane permeability to K+ is much higher than to Na+ due to open K+ leak channels, so the RMP lies close to the K+ equilibrium potential (Ek, calculated via the Nernst equation, ~ -90 mV) but is slightly less negative (~ -70 mV in neurons) due to some Na+ leak and the electrogenic contribution of the Na+/K+ ATPase (which pumps 3 Na+ out and 2 K+ in, extruding one net positive charge). The Goldman-Hodgkin-Katz (GHK) equation more accurately predicts RMP by accounting for permeabilities of multiple ions (K+, Na+, Cl-). Clinical relevance: Hyperkalemia depolarizes RMP (brings it closer to threshold), initially increasing excitability but with sustained depolarization inactivates Na+ channels, leading to decreased excitability and arrhythmias (peaked T waves, widened QRS). Hypokalemia hyperpolarizes RMP, decreasing excitability, causing muscle weakness and arrhythmias. Cardiac glycosides (digoxin) inhibit Na+/K+ ATPase, indirectly affecting Ca2+ handling and contractility. Local anesthetics and antiarrhythmics act on Na+ channels influenced by RMP. Understanding RMP is foundational for action potential generation, cardiac electrophysiology, and neuromuscular pharmacology, frequently tested via ECG changes with electrolyte disturbances and channelopathies (e.g., periodic paralysis, Long QT syndrome).
Sources
- Guyton and Hall Textbook of Medical Physiology
- Costanzo Physiology
- First Aid for the USMLE Step 1
- Boron & Boulpaep Medical Physiology
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