Regulation of agonist-evoked [Ca²⁺](i) oscillation by intracellular Ca²⁺ and Ba²⁺ in AR42J cells

Measurements of intracellular Ca²⁺ ([Ca²⁺](i)) and intracellular Ba²⁺ ([Ba²⁺](i)) in single AR42J cells were used to evaluate the effect of [Ca²⁺](i) and [Ba²⁺](i) on agonist-evoked [Ca²⁺](i) oscillations. Variations in [Ca²⁺](i) and [Ba²⁺](i) were imposed by gradual activation of entry through voltage-activated Ca²⁺ channels (VACC) present in the plasma membrane of these cells. Activation by high K⁺ was followed by partial inactivation of the channels and stabilization of [Ca²⁺](i) at a new steady-state level depending on the extent of depolarization. Activation by BAY K 8644 was followed by complete inactivation and return of [Ca²⁺](i) to resting levels. Ba²⁺ activated the channels and entered the cells but could not be removed from the cytosol by cellular Ca²⁺ pumps. The use of channel blockers and the ability to increase [Ca²⁺](i) and [Ba²⁺](i) by channel activation during [Ca²⁺](i) oscillations showed that VACC do not contribute to or are activated during agonist-stimulated Ca²⁺ oscillation in this cell type. Graded activation of VACC showed that an increase in [Ca²⁺](i) between the spikes to below 200 nM increased the frequency of the oscillation. Further increase in [Ca²⁺](i) caused gradual reduction in the frequency. At [Ca²⁺](i) above 500 nM, [Ca²⁺](i) oscillations were inhibited. The inhibitory but not the stimulatory effects of [Ca²⁺](i) on the oscillations can be mimicked by [Ba²⁺](i). These observations suggest that [Ca²⁺](i) levels between the spikes play an important role in regulating the oscillations.