Inward Rectifier Potassium Channels in Resistance Arteries

Abstract

Inward rectifier potassium channels (K_ℝ) are present in cardiac muscle, skeletal muscle, and in some vascular smooth muscle cells. The term inward rectification arises from the observation that when the membrane potential of the cell is controlled (for example, by voltage clamp of the cell) then the K_ℝ channel will pass larger inward currents (movement of potassium ions from the extracellular solution into the cell), than outward currents (from the cell to the extracellular solution). However, it is important to note that in physiological potassium gradients and at physiological membrane potentials there will be an electrochemical gradient favouring potassium ions to leave the cell, and the inward rectifier will therefore normally pass an outward, hyperpolarizing membrane current. Many other potassium channels are affected by the voltage across the cell membrane, for example both voltage-activated and calcium-activated potassium channels become more active as the membrane potential becomes more positive. The inward rectifier is unusual in becoming less active as the membrane is depolarized, and more active as the membrane potential is hyperpolarized. In fact this property of inward rectification is central to many of the proposed functions of the channel. Thus in skeletal and cardiac muscle, the suggested roles of the K_ℝ include generation of the resting membrane potential, preventing potassium loss from the fibers during long duration action potentials, providing a route for potassium uptake into the cell from the transverse tubules, and preventing hyperpolarization of the membrane potential to values more negative than the potassium equilibrium potential by an active electrogenic Na⁺/K⁺ ATPase (4). These functions of the K_ℝ may also be important in vascular smooth muscle, for example small arteries subjected to physiological transmural pressures depolarize and develop myogenic tone (1,3). The membrane potential of smooth muscle cells in myogenic arteries is around −40 to −50 mV, and the K_ℝ will limit the outward movement of potassium ions from the cell under these depolarized conditions. Because K⁺ must be accumulated into the cell against its electrochemical gradient, mainly by the Na⁺/K⁺ ATPase, a process associated with hydrolysis of ATP, minimizing K⁺ loss during depolarization is of obvious value in preserving the cell’s energy resources.