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 guineapig cerebellar slices were studied using the macropatch clamp technique. Pressure did not significantly alter the single somatic Naf spike parameters or the frequency of regular Na+ spike firing. When Na+ currents were blocked by 0.5-1 mu M 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 Kf 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 mu M 4-AP, whereas in the presence of 5 mM 4-AP the pattern was insensitive to pressure. A high [Ca2+], 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+], 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 Kf currents induce depression of dendritic excitability at pressure.