EFFECTS OF VERATRIDINE ON NA AND CA CURRENTS IN FROG SKELETAL-MUSCLE

1. Voltage-clamp experiments were performed to determine the effects o f veratridine on Na and Ca currents in frog skeletal muscle fibres. 2. Veratridine (1 mu M) did not affect the kinetics of the fast Na curre nt but it did induce a slowly inactivating tetrodotoxin-sensitive inwa rd current that was apparent after Na current inactivation. This slow current had a peak amplitude of 6.7 +/- 0.7 mu A/cm(2) at -20 mV and d ecayed monoexponentially with a time constant of 606 +/- 77 ms. 3. The slow current had a voltage-dependence for activation that was similar to that of the fast Na current. Single depolarizing prepulses that in duced complete inactivation of the fast Na channels, prevented develop ment of the slow current. Trains of brief depolarizations at increasin g frequencies increased the amplitude of the slow current. These resul ts suggest that the slow current may be mediated by veratridine modifi ed Na channels that must be in the open position. 4. The low concentra tion of veratridine (1 mu M) did not affect the Ca current, while 100 mu M veratridine reversibly suppressed the Ca current and shifted its peak current-voltage relation towards more negative potentials. Thus, veratridine appears not to be a selective fast Na channel modifier as it may also alter Ca channel gating properties in skeletal muscle fibr es.