KINETIC AND PHARMACOLOGICAL PROPERTIES OF HIGH-THRESHOLD AND LOW-THRESHOLD CALCIUM CHANNELS IN PRIMARY CULTURES OF RAT HIPPOCAMPAL-NEURONS

The kinetic, permeability and pharmacological properties of Ca currents were investigated in primary cultures of rat hippocampal neurons. The low-voltage-activated (LVA) Ca current turned on positive to -60 mV and fully inactivated in a voltage-dependent way. This current was depressed by nickel (Ni, 40-mu-M) and amiloride (500-mu-M) and was insensitive to omega-conotoxin (omega-CgTx) (4-mu-M) and to the Ca agonist Bay K 8644 (5-mu-M). The high-voltage-activated (HVA) Ca current turned on positive to -40 mV and inactivated slowly and incompletely. This current was much less sensitive than the LVA current to Ni and amiloride but more sensitive to cadmium. omega-CgTx blocked only partially this current (about 50%) in an irreversible way. Bay K 8644 had a clear agonistic action almost exclusively on the omega-CgTx-resistant HVA current component. The present results suggest that the HVA channels, quite homogeneous for their kinetic properties and sensitivity to holding potentials, can be pharmacologically separated in two classes: (i) omega-CgTx-sensitive and Bay-K-8644-insensitive (omega-S/BK-1) and (ii) omega-CgTx-insensitive and Bay-K-8644-sensitive (omega-I/BK-S), the latter displaying a stronger Ca-dependent inactivation.