Spontaneous Na+ and Ca2+ spike firing of cerebellar Purkinje neurons at high pressure.

The effects of high pressure (up to 10.1 MPa) on the spontaneous firing of Purkinje neurons in guinea-pig cerebellar slices were studied using the macropatch clamp technique. Pressure did not significantly alter the single somatic Na+ spike parameters or the frequency of regular Na+ spike firing. When Na+ currents were blocked by 0.5-1 microM tetrodotoxin (TTX), a pressure of 10.1 MPa slightly reduced the dendritic Ca2+ spike amplitude to 90.2+/-3.1% of its control value, and slowed its kinetics. The effects of pressure on the single Ca2+ spike were even less prominent when K+ currents were blocked by 5 mM 4-aminopyridine (4-AP). Pressure prolonged the active period of Ca2+ spike firing to 152.2+/-10.4% of the control value. Within the active period pressure increased the inter-spike interval to 164.9+/-8.7% and suppressed the typical firing of doublets. The latter changes were reversed by a high extracellular potassium concentration ([K+]o) and 1 microM 4-AP, whereas in the presence of 5 mM 4-AP the pattern was insensitive to pressure. A high [Ca2+]o reduced the firing frequency and suppressed doublet firing in a manner reminiscent of the pressure effect, but these changes could not be reversed by 4-AP. A low [Ca2+]o slightly increased the firing of doublets. These results show that the single somatic Na+ spike is insensitive and the dendritic Ca2+ spike is only mildly sensitive to pressure. However, alterations in Ca2+ spike firing pattern suggest that modulation of dendritic K+ currents induce depression of dendritic excitability at pressure.