LOW BA2-TYPE CA2+ CHANNELS IN HIPPOCAMPAL-NEURONS - PHYSIOLOGICAL IMPLICATIONS( AND CA2+ INDUCE A SUSTAINED HIGH PROBABILITY OF REPOLARIZATION OPENINGS OF L)

Openings of single L-type Ca2+ channels following repolarization to ne gative membrane potentials from a depolarizing step (repolarization op enings, ROs) have been described previously in brain cell preparations . However, these ROs have been reported to occur only infrequently. He re we report that the frequency of ROs in cell-attached patches of cul tured rat hippocampal neurons can be increased dramatically by lowerin g the pipette Ba2+ concentration to 20 mM from the usual 90-110 mM. Th is increased opening probability can last for hundreds to thousands of milliseconds following repolarization. Current-voltage analyses of op en probability show that the depolarization pulse threshold for induci ng ROs in 20 mM Ba2+ is -10 to 0 mV but that the probability of ROs re aches maximal levels following depolarizing pulses that approach the a pparent null (equilibrium) potential for Ba2+. Comparable current-volt age curves in 110 mM Ba2+ form a more positive holding potential (-50 mV) indicate that membrane surface charge screening accounts for some, but not all, of the effect of lowering the Ba2+ concentration. Conseq uently, current-dependent inactivation or some other ion-dependent mec hanism (e.g., ion binding inside the pore) also appears to regulate th is potentially major pathway of Ca2+ entry. A high probability of ROs also can be induced under relatively physiological conditions (5-ms de polarizing steps, 2-5 MM Ca2+ in the pipette). Thus, the high open pro bability state at negative potentials may underlie the long Ca2+ tail currents in hippocampus that were described previously and appears to have major implications for physiological functions (e.g., the slow Ca 2+-dependent afterhyperpolarization), particularly in brain neurons.