Long-lasting in vivo inotropic effects of the K(+) channel blocker 3,4-diaminopyridine during fatigue-inducing stimulation.
Blocking K(+) channels with aminopyridines enhances muscle contractile performance in vitro, but the improvements are relatively short-lasting during fatigue-inducing stimulation. We hypothesized that in vivo inotropic actions persist over long periods of fatigue-inducing stimulation. The effects of 3,4-diaminopyridine (DAP) were evaluated for rat extensor digitorum longus (EDL) muscle. DAP increased twitch force by 105%. There was a significant leftward shift in the force-frequency relationship, with force values being increased at frequencies up to and including 20 HZ. During repetitive fatigue-inducing 20-HZ stimulation, DAP-induced force increases were large and persisted significantly for at least 30 minutes. Thus, DAP substantially improves contractile performance of EDL muscle in vivo for much longer periods during fatigue-inducing contractions than in vitro. These data provide support for a potential role for aminopyridines as inotropic agents in applications such as functional electrical stimulation, in which low to medium stimulation frequencies are typically utilized.
Van Lunteren
Erik
E
Department of Pulmonary Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA. exv4@cwru.edu
Moyer
Michelle
M
Pollarine
Jennifer
J
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D002316:Cardiotonic Agents; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor / Q000187:drug effects; D007537:Isometric Contraction; D018763:Muscle Fatigue / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D000077770:Amifampridine