Distinct kinetics of cloned T-type Ca2+ channels lead to differential Ca2+entry and frequency-dependence during mock action potentials

Voltage-dependent activity around the resting potential is determinant in n euronal physiology and participates in the definition of the firing pattern . Low-voltage-activated T-type Ca2+ channels directly affect the membrane p otential and control a number of secondary Ca2+-dependent permeabilities. W e have studied the ability of the cloned T-type channels (alpha 1G,H,I) to carry Ca2+ currents in response to mock action potentials. The relationship between the spike duration and the current amplitude is specific for each of the T-type channels, reflecting their individual kinetic properties. Typ ically the charge transfer increases with spike broadening, but the total C a2+ entry saturates at different spike durations according to the channel t ype: 4 ms for alpha 1G; 7 ms for alpha 1H; and > 10 ms for alpha 1I channel s. During bursts, currents are inhibited and/or transiently potentiated acc ording to the alpha 1 channel type, with larger effects at higher frequency . The inhibition may be induced by voltage-independent transitions toward i nactivated states and/or channel inactivation through intermediate closed s tates. The potentiation is explained by an acceleration in the channel acti vation kinetics. Relatively fast inactivation and slow recovery limit the a bility of alpha 1G and alpha 1H channels to respond to high frequency stimu lation (> 20 Hz). In contrast, the slow inactivation of alpha 1I subunits a llows these channels to continue participating in high frequency bursts (10 0 Hz). The biophysical properties of alpha 1G, H and I channels will theref ore dramatically modulate the effect of neuronal activities on Ca2+ signall ing.