Regulation of a volume-sensitive anion channel in rat pancreatic beta-cells by intracellular adenine nucleotides.

Abstract

1. The patch-clamp technique in the whole-cell configuration was used to measure the effects of intracellular adenine nucleotides on activity of the volume-sensitive anion channel in single, isolated rat pancreatic beta-cells. 2. In the absence of intracellular nucleotides, swelling of cells with a hypertonic pipette solution failed to activate the conductance. Addition of ATP over the range 2-10 mM maintaining the same degree of hypertonicity caused a progressive activation of the conductance. An increase in ATP produced a similar activation of the conductance in non-swollen cells, albeit with reduced current amplitudes. 3. Activation of the conductance was also observed in the presence of ATPgammaS, adenylyl imidophosphate (AMP-PNP), ADP, diadenosine tetraphosphate and GTPgammaS. Neither ADP nor GDPbetaS inhibited activation of the conductance by ATP. 4. It is concluded that activity of the beta-cell volume-sensitive anion channel can be modulated by changes in intracellular concentrations of ATP within the physiological concentration range by a mechanism that does not require nucleotide hydrolysis. Activity of the channel does not appear to be modulated by a G protein-coupled mechanism.