title: Modulation of diaphragm action potentials by K(+) channel blockers.
abstract: 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 degrees C. 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.
authors.affiliation: Department of Medicine, Cleveland VA Medical Center, Pulmonary Section, 111J(W), 10701 East Boulevard, Cleveland, OH 44106, USA. exv4@po.cwru.edu
authors.forename: E
authors.initials: E
authors.lastname: van Lunteren
authors.forename: M
authors.initials: M
authors.lastname: Moyer
authors.forename: T E
authors.initials: TE
authors.lastname: Dick
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
chemical_list: D026902:Potassium Channel Blockers