MULTIPLE-CHANNEL TYPES CONTRIBUTE TO THE LOW-VOLTAGE-ACTIVATED CALCIUM CURRENT IN HIPPOCAMPAL CA3 PYRAMIDAL NEURONS

Hippocampal neurons exhibit low-voltage-activated (LVA) and high-volta ge-activated (HVA) calcium currents. We character ized the LVA current by recording whole-cell Ca2+ currents from acutely isolated rat hippo campal CA3 pyramidal neurons in 2 mM Ca2+. Long depolarizing steps to -50 mV revealed two components to the LVA current: transient and susta ined. The transient phase had a fast decay time constant of 59 msec. T he sustained phase persisted throughout the depolarization, even for s teps lasting several seconds. The transient current was inhibited by t he classic T-type channel antagonists Ni2+ and amiloride. The anticonv ulsant phenytoin preferentially blocked the sustained phase, but ethos uximide had no effect. Steady-state inactivation of the transient comp onent was half-maximal at -80 mV. Nimodipine, an L-type channel antago nist, partly inhibited the sustained current. BayK-8644, an L-type cha nnel agonist, potentiated the sustained current. Calciseptine, another L-type channel antagonist, inhibited the sustained component. omega-C onoloxin-MVIIC, a nonselective toxin for HVA channels, had no effect o n either of the LVA current components. omega-Grammotoxin-SIA, another nonselective toxin, partially inhibited the sustained component. The voltage dependence of activation of the nimodipine-sensitive current c ould be fit with a single Boltzmann, consistent with a homogenous popu lation of L-type channels in CA3 neurons. Half-maximal activation of t he nimodipine-sensitive current occurred at -30 mV, considerably more negative than the remaining HVA current. These results suggest that in physiologic Ca2+ more than one type of Ca2+ channel contributes to th e LVA current in CA3 neurons. The transient current is carried by T-ty pe channels. The sustained current is carried, at least in part, by di hydropyridine-sensitive channels. Thus, the designation ''low-voltage- activated'' should not be limited to T-type channels. These findings c hallenge the traditional designation of L-type channels as exclusively HVA and reveal a possible role in subthreshold Ca2+ signaling.