Agonist-induced frequency modulation of Ca2+ oscillations in salt gland secretory cells

Oscillations in intracellular calcium concentration ([Ca2+]i) induced by the acetylcholine analogue carbachol (CCh) were characterized by microspectrofluorimetry of fura-2 in single secretory cells from the avian salt gland. The frequency of oscillations increased in graded fashion with [CCh] between 25 nM (2.7 +/- 0.6 min-1) and 250 nM (11.8 +/- 1.4 min-1), whereas the amplitude of the spikes was independent of [CCh]. An interperiod return to prestimulatory [Ca2+]i was generally seen only at very low (25 nM) CCh. Between 50 and 250 nM CCh, oscillations were associated with sustained elevated [Ca2+]i levels. The amplitude of the oscillatory spikes was found not to exceed that of initial spikes arising from prestimulatory [Ca2+]i, despite the dose-dependent [effective concentration at 50% (EC50) = 200 nM CCh] sustained rise in [Ca2+]i. At 1 microM CCh, oscillations gave way to a maximal sustained increase in [Ca2+]i. Reduction of [Ca2+]o to 1.5 microM during an oscillatory train or blockage of Ca2+ influx with Ni+ resulted in a reduction in sustained Ca2+i levels and in frequency, but not amplitude, of oscillations. A relationship between the sustained partial rise in [Ca2+]i derived from Ca2+ influx and the oscillatory frequency at a given [CCh] was further indicated by the lower frequency (P less than 0.01) of the early spikes in a train when interspike [Ca2+]i initially returned to near-basal levels. In some cells, oscillations were slow enough (less than 2 min-1) to resolve an interperiod of elevated baseline [Ca2+]i, showing that the latter can occur independent of the repetitive Ca2+ spikes. (ABSTRACT TRUNCATED AT 250 WORDS)