Ionophore A23187 can mimick the changes in membrane permeability that occur during acetylcholine-stimulation of pancreatic acinar secretion

Abstract

Acetylcholine (ACh) released from vagal terminals increases the permeability of the pancreatic acinar membrane to Na⁺ and Ca²⁺ ions. In this report, we compare the induced changes in intracellular Na⁺ and Ca²⁺ electrode potentials (E_Na and E_Ca) due to ACh-stimulation of acini with those observed during stimulation with the calcium ionophore, A23187, which mimicks the action of ACh on pancreatic secretion. Stimulation with ACh concentrations varying from 10⁻⁸ to 10⁻⁵ M and with A23187 concentrations of 10⁻⁶ and 10⁻⁵ M caused parallel increases in cytosolic Ca²⁺ and Na⁺ ([Ca]_i, [Na]_i). The magnitude of the increases in [Ca]_i and [Na]_i due to A23187-stimulation further indicate that when presented with a calcium challenge the acinar cells continue to regulate [Ca]_i close to physiological levels and suggest that the observed increases in ionized calcium could reflect much larger increases in complexed Ca²⁺. ACh-stimulation following removal of either extracellular Na⁺ or Ca²⁺ ions, eliminated the intracellular increases found when the removed ions is present, but did not affect the increases usually found with the other ion. The independence of the permeability changes to either the presence of Ca²⁺ or Na⁺ indicates the ACh-induced currents carried by Na⁺ and Ca²⁺ are also independent. The selective translocation of Na⁺ and Ca²⁺ during acetylcholine-stimulation in a manner analogous to the changes observed when ionophore A23187 was used as stimulus, indicates the ability of the activated acinar membrane to function as an ionophore.