Potassium currents modulation of calcium spike firing in dendrites of cerebellar Purkinje cells

The pattern of sustained Ca2+ spike firing was Introduction investigated, using macropatch clamp and intracellular recordings, in guinea pig cerebellar Purkinje cells. Under our standard experimental conditions (30 degrees C, 5 mM [K+](0), 2 mM [Ca2+](0), 1 mu M tetrodotoxin), each firing period started with uniform firing and gradually turned into a doublet pattern with a large spike afterhyperpolarization (AHP) between the doublers. Macropatch clamp recordings from localized dendritic regions revealed that each doubler is composed of two similar inward current deflections. This result indicated, for both peaks, an active process in the recording site and contradicted the possibility that they reflect firing in two completely separated dendritic regions. When [K+], was increased the transition to a doublet pattern occurred earlier and the doublets became more pronounced. A similar but more prominent effect occurred following application of 1-10 mu M 4-aminopyridine, which also reduced the threshold, increased the spike amplitude, and shortened the initial delay of evoked Ca2+ spike firing. In contrast, membrane depolarization, increased [Ca2+](0), and application of quinidine (but not apamine) markedly suppressed the generation of doublet pattern. During uniform initial firing, a short hyperpolarizing pulse that mimicked a large AHP induced a subsequent doublet. A short depolarizing pulse following a sing le spike induced an artificial doublet followed by a large AHP. These results indicate that the pattern of Ca2+ spike firing in the dendrites of Purkinje cells is dynamically modulated by a highly aminopyridine-sensitive Kf current, and probably also by a Ca2+ -activated potassium current.