Inotropic Effects of K+ Channel Blocker 3,4‐Diaminopyridine (DAP) In Vivo

Blocking K+ channels with aminopyridines produces considerable improvements in muscle contractile function in vitro. We tested the hypothesis that intropic actions also occur in vivo under conditions where possible systemic effects of these agents (eg. on blood pressure and muscle blood flow) or alterations in neurotransmission may modulate responses. The effect of DAP was evaluated on extensor digotorum longus (EDL) isometric force elicited by nerve stimulation in anesthetized rats. DAP increased twitch force from 83 to 177 g (P<0.001). There was a significant (P=0.024) leftward shift in the force‐frequency relationship, with force values being significantly increased at frequencies up to and including 20 Hz. During repetitive fatigue‐inducing 20 Hz train stimulation, the DAP‐induced force increases persisted for over 30 minutes. These data indicate that DAP indeed substantially improves isometric contractile performance of EDL muscle in vivo, strengthening the potential role for aminopyridines as inotropic agents in applications such as functional electrical stimulation in which low to medium stimulation frequencies are typically utilized. SUPPORT: VA Research Service, NHLBI