A blocker-resistant, fast-decaying, intermediate-threshold calcium currentin palaeocortical pyramidal neurons

The whole-cell patch-clamp technique was used to record Ca2+ currents in ac utely dissociated neurons from layer II of guinea-pig piriform cortex (PC). Ba2+ (5 mm) was used as charge carrier. In a subpopulation of layer II cel ls (approximate to 22%) total Ba2+ currents (I(Ba)s) displayed a high degre e (> 70%) of inactivation after 300 ms of steady depolarization. The applic ation of L-, N- and P/Q-type Ca2+-channel blockers to these high-decay I(Ba )s left their fast inactivating component largely unaffected. The inactivat ion phase of the blocker-resistant, fast-decaying I-Ba thus isolated had a bi-exponential time course, with a fast time constant of approximate to 20 ms and a slower time constant of approximate to 100 ms at voltage levels po sitive to -10 mV. The voltage dependence of activation of the blocker-resis tant, fast-decaying I-Ba was shifted by approximate to 7-9 mV in the negati ve direction in comparison with those of other pharmacologically and/or kin etically different high-voltage-activated Ca2+ currents. We named this bloc ker-resistant, fast-decaying, intermediate-threshold current I-Rfi. The amp litude of I-Rfi decreased only slightly (by approximate to 9%) when extrace llular Ca2+ was substituted for Ba2+, in contrast with that of slowly decay ing, high-voltage-activated currents, which was reduced by approximate to 4 1% on average. Moreover, I-Rfi was substantially inhibited by low concentra tions of Ni2+ (50 mu m). We conclude that I-Rfi, because of its fast inacti vation kinetics, intermediate threshold of activation and resistance to org anic blockers, represents a definite, identifiable Ca2+ current different f rom classical high-voltage-activated currents and clearly distinguishable f rom classical I-T. The striking similarity found between I-Rfi and Ca2+ cur rents resulting from heterologous expression of alpha(1E)-type channel subu nits is discussed.