Fig. 4. NA Blockade of T-type channels is state-dependent.

A) Left panel, traces of current recorded with the protocol depicted above to maintain the T-type channels in the closed state. A test pulse of −20 mV was applied with at = 120 s from a HP = −90 mV. Right panel, normalized current was plotted against time; white and grey bars represent time to exposure to control solution and NA, respectively. Note that ~ 25% of inward current amplitude was reduced by NA. B) Effect of NA on inactivated state of T-type channels. Left panel, current recorded in response to a depolarization to −20 mV from a 400 ms hyperpolarized pulse to −90 mV. Cells were held at −20 mV to maintain the channels inactivated. Right panel normalized current versus time of exposure to NA. Note a reduction of more than 50% in presence of the drug by using the inactivated state protocol. C) Left panel, blockade of T-type currents by NA in open state. Cells were clamped at −90 mV during the whole experiment with a depolarization to −20 mV with a Δt = 5 s. Inset, continuously stimulated cells with the protocol previously described during 500 s without drug did not modify the currents during the whole experiment. Right panel, normalized current shows a decrement in the amplitude of the current of more than 50% during the time of exposure. Error bars represent SEM, (n = 6). Note that in the three conditions 85% of the original current was recovered by washing the drug.