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The leaner (tg^la) mouse mutation occurs in the gene encoding the voltage-activated Ca²⁺channel α_1A subunit, the pore-forming subunit of P/Q-type Ca²⁺ channels. This mutation results in dramatic reductions in P-type Ca²⁺ channel function in cerebellar Purkinje neurons of tg^la/tg^la mice that could affect intracellular Ca²⁺ signaling. We combined whole cell patch-clamp electrophysiology with fura-2 microfluorimetry to examine aspects of Ca²⁺ homeostasis in acutely dissociated tg^la/tg^la Purkinje cells. There was no difference between resting somatic Ca²⁺ concentrations in tg^la/tg^la cells and in wild-type (+/+) cells. However, by quantifying the relationship between intracellular Ca²⁺ elevations and depolarization-induced Ca²⁺influx, we detected marked alterations in rapid calcium buffering between the two genotypes. Calcium buffering values (ratio of bound/free ions) were significantly reduced in tg^la/tg^la (584 ± …