Inotropic Effects of the ${\rm K}^{+}$ Channel Blocker 3,4-Diaminopyridine: Differential Responses of Rat Soleus and Extensor Digitorum Longus

The K⁺ channel blocker 3,4-diaminopyrindine (DAP) increases diaphragm force, use of which could potentially improve muscle performance during functional neuromuscular stimulation. To determine the extent of hindlimb muscle force augmentation, and delineate whether DAP effects vary in muscles comprised of mainly slow versus fast fibers, rat soleus, extensor digitorum longus (EDL) and diaphragm muscle samples were studied in vitro. DAP increased force of all three muscles, but at high concentrations the force increases were transient and were followed by declines in force below baseline. The maximum DAP-induced twitch force increase was smaller for soleus (38 plusmn 7%) than both EDL (94 plusmn 12%) (P<0.05) and diaphragm (93 plusmn 13%) (P<0.01). During fatigue-inducing 20 Hz stimulation (tested at an intermediate DAP concentration), force of soleus muscle remained significantly elevated by DAP for the entire testing period, force of DAP-treated EDL muscle rapidly declined to values in untreated muscle, and force of DAP-treated diaphragm had an intermediate force-time profile. Muscles varied in extent to which isometric contractile kinetics were altered by DAP. Thus, the K⁺ channel blocker DAP improves contractile performance of limb muscles, but the profile of improvement is distinct between the soleus and EDL muscles. Nomenclature) 4-AP: 4-aminopyridine) DAP: 3,4-diaminopyridine) EDL: extensor digitorum longus