Active components of excitability in K-depolarized ventricular muscle

The steady-state and dynamic characteristics of excitability were assessed in isolated guinea pig papillary muscles depolarized with elevated K+]o to resting potentials near -60 mV. Transmembrane potentials were recorded from fibers during application of low-amplitude current pulses used to analyze net changes in active membrane components of excitability in terms of elicited local responses and measure threshold current (Ith). Generated local responses were blocked entirely by tetrodotoxin and lidocaine, which increased steady-state Ith by more than 200%. In the absence of Na+ channel-blocking agents, local responses showed marked but characteristic attenuation in a time- and voltage-dependent manner by preceding subthreshold depolarizations, which concomitantly reduced excitability. However, local responses and excitability were also modulated by small changes in Ca2+]o (+/- 0.7 mmol) and reduced by exposure to slow channel blockers and to Cs+. Thus these data suggest that while the Na+ channel is the primary active component of excitability in partially depolarized ventricular muscle, Ca2+ -mediated and Cs+ -sensitive conductances may also participate, although to a lesser extent. These findings may help explain the frequency-dependence of excitability and conduction under conditions of ischemia in the intact heart.