Modulation of diaphragm action potentials by K+ channel blockers

K+ channels regulate diaphragm contractility. The present study examined the electrophysiological mechanisms accounting for diversity among K+ channel blockers in their inotropic actions on the diaphragm. Rat diaphragmatic muscle fibers were recorded intracellularly in vitro at 37 degreesC. Apamin and charybdotoxin (Ca2+-activated K+ channel blockers) did not alter resting membrane potential or action potentials. Glibenclamide (ATP-sensitive K+ channel blocker) slowed action potential repolarization by 12% (P <0.05) and increased action potential area by 25% (P < 0.005). Tetraethylammonium (which blocks several types of K+ channels) increased action potential overshoot by 20% (P < 0.01) and prolonged action potential rise time by 17% (P < 0.02). 4-Aminopyridine and 3,4-diaminopyridine (which also block several types of K+ channels) slowed action potential repolarization by 163% (P < 0.0001) and 253% (P < 0.0001), and increased action potential area by 183% (P < 0.0001) and 298% (P < 0.0001), respectively. Slowing of repolarization for the aminopyridines was especially marked at voltages approaching resting membrane potential, thereby changing action potential repolarization from a first to a second order decay. Previously reported variability in inotropic effects among K+ channel blockers correlated significantly with the extent to which they slowed action potential repolarization and increased action potential area, but not with changes in other action potential properties. (C) 2001 Elsevier Science B.V. All rights reserved.