Figure 2.

Inward-rectifier K⁺ channels are activated by increases in external K⁺. (A) In situ, raising K⁺ to <20 mM causes rapid and substantial vasodilation of pressurized (40 mm Hg) PAs due to K_IR channel activation; further increases in K⁺ drive membrane depolarization and constriction. Trace from [67]. (B) The SM of PAs behaves as a K⁺ electrode with increasing concentrations of extracellular K⁺. Experimentally observed membrane potential (V_m) data (from [26,37,89]) are shown versus the potassium equilibrium potential (E_K) predicted by the Nernst equation. At 3 mM K⁺, V_m is depolarized relative to E_K due to myogenic inward cation currents. Raising K⁺ activates K_IR channels, and the resultant K⁺ efflux effectively locks V_m at E_K. (C) Hypothetical K_IR current-voltage relationship (left) and illustration (right) showing that at basal extracellular K⁺ (3 mM) the pore of the K_IR channel is blocked by Mg²⁺ or large cationic polyamines. Under these conditions (assuming 140 mM [K⁺]_i), E_K is -103, which is highly negative compared to the resting V_m of SM (approximately -35 to -40 mV) at the physiological intravascular pressure of 40 mmHg. The strong driving force for cation efflux under these conditions leads to blockade of the channel pore by the larger cations, resulting in very little channel activity. (D) When [K⁺]_o is elevated to 8 mM (e.g., when released from the astrocytic endfoot during NVC), intracellular blockade of the channel is relieved. Channel unblock allows K⁺ to exit the cell, driving V_m to the new E_K—where it will remain until the extracellular K⁺ is cleared—and leading to substantial vasodilation.