Cat ventricular muscle treated with D600: effects on calcium and potassium currents

In single sucrose-gap experiments on cat ventricular muscle strands stimulated with 300 ms pulses at 0.33 Hz, 2 microM-D600 reduced the Ca-dependent slow inward current (ICa) by 50% within 5 min and more than 90% in 90-120 min. The late outward current was reduced by up to 30%. During the exposure to D600, Ca channels could be unblocked by hyperpolarizing pulses and blocked again by stimulation with depolarizing pulses. Since the degree of unblocking depended on voltage, and the degree of blocking depended on stimulation pattern, ICa amplitude could be rapidly manipulated to probe the dependence of K conductance on ICa. Under control conditions, an increase in stimulation rate from 0.02 to 1 Hz reduced ICa by 15% and increased the late outward current by a smaller amount. During exposure to D600, a similar intervention provoked a 60% reduction in ICa, but a control-like increase in the late outward current. Two other series of experiments failed to disclose a link between ICa and K conductance: when a block of Ca channels was reimposed following their unblocking, the outward currents were independent of ICa amplitude. Unblock-block experiments also provided information on the extent of steady-state ICa at 0 mV. The fraction of Ca channels not undergoing inactivation appears to be very small. During full D600 block, the inward peak of the current wave form is broad and very much delayed in comparison with pre-drug currents or currents on the first pulse following unblocking. A similar wave form was recorded in D600-treated ventricular myocytes from cat but not guinea-pig. The likely explanation is that D600 unmasks a small transient outward current in cat ventricle.