Long‐lasting in vivo inotropic effects of the K+ channel blocker 3,4‐diaminopyridine during fatigue‐inducing stimulation |
| |
Authors: | Erik Van Lunteren MD Michelle Moyer MS Jennifer Pollarine BS |
| |
Institution: | Department of Pulmonary Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center and Case Western Reserve University, Cleveland, Ohio 44106, USA |
| |
Abstract: | 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. Muscle Nerve 38: 1616–1622, 2008 |
| |
Keywords: | diaphragm K+ channel muscle fatigue skeletal muscle |
|
|