LONG-LASTING IN VIVO INOTROPIC EFFECTS OF THE K+ CHANNEL BLOCKER 3,4-DIAMINOPYRIDINE DURING FATIGUE-INDUCING STIMULATION

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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

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