Transient rise in intracellular calcium produces a long-lasting increase in plasma membrane calcium pump activity in rat sensory neurons

The plasma membrane Ca²⁺ ATPase (PMCA) plays a major role in clearing Ca²⁺ from the neuronal cytoplasm. Calmodulin stimulates PMCA activity and for some isoforms this activation persists following clearance of Ca²⁺ owing to the slow dissociation of calmodulin. We tested the hypothesis that PMCA-mediated Ca²⁺ efflux from rat dorsal root ganglion (DRG) neurons in culture would remain stimulated following increases in intracellular Ca²⁺ concentration ([Ca²⁺]_i). PMCA-mediated Ca²⁺ extrusion was,recorded following brief trains of action potentials using indo-l-based photometry in the presence of cyclopiazonic acid. A priming stimulus that increased [Ca²⁺]_i to 506 ± 28 nM (>15 min) increased the rate constant for [Ca²⁺]_i recovery by 47 ± 3%. Ca²⁺ clearance from subsequent test stimuli remained accelerated for up to an hour despite removal of the priming stimulus and a return to basal [Ca²⁺]_i. The acceleration depended on the magnitude and duration of the priming [Ca²⁺]_i increase, but was independent of the source of Ca²⁺. Increases in [Ca²⁺]_i evoked by prolonged depolarization, sustained trains of action potentials or activation of vanilloid receptors all accelerated Ca²⁺ efflux. We conclude that PMCA-mediated Ca²⁺ efflux in DRG neurons is a dynamic process in which intense stimuli prime the pump for the next Ca²⁺ challenge.