Regulation of a volume-sensitive anion channel in rat pancreatic beta-cells by intracellular adenine nucleotides.
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.
School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
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Miley
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Brown
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Best
D000227:Adenine Nucleotides / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D004553:Electric Conductivity; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000227:Adenine Nucleotides; D000838:Anions; D007473:Ion Channels; C034883:guanosine 5'-O-(2-thiotriphosphate); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate