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 μM 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 μM 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.