Regulation of maxi-K+ channels on pancreatic duct cells by cyclic AMP-dependent phosphorylation |
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Authors: | M A Gray J R Greenwell A J Garton B E Argent |
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Institution: | (1) Department of Physiological Sciences, University Medical School, NE2 4HH Newcastle upon Tyne, UK;(2) Present address: Department of Biochemistry and Genetics, University Medical School, NE2 4HH Newcastle upon Tyne, UK |
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Abstract: | Summary Using the patch-clamp technique we have identified a Ca2+-sensitive, voltage-dependent, maxi-K+ channel on the basolateral surface of rat pancreatic duct cells. The channel had a conductance of 200 pS in excised patches bathed in symmetrical 150mm K+, and was blocked by 1mm Ba2+. Channel openstate probability (P
o
) on unstimulated cells was very low, but was markedly increased by exposing the cells to secretin, dibutyryl cyclic AMP, forskolin or isobutylmethylxanthine. Stimulation also shifted theP
o
/voltage relationship towards hyperpolarizing potentials, but channel conductance was unchanged. If patches were excised from stimulated cells into the inside-out configuration,P
o
remained high, and was not markedly reduced by lowering bath (cytoplasmic) Ca2+ concentration from 2mm to 0.1 m. However, activated channels were still blocked by 1mm Ba2+. ChannelP
o
was also increased by exposing the cytoplasmic face of excised patches to the purified catalytic subunit of cyclic AMP-dependent protein kinase., We conclude that cyclic AMP-dependent phosphorylation can activate maxi-K+ channels on pancreatic duct cells via a stable modification of the channel protein itself, or a closely associated regulatory subunit, and that phosphorylation alters the responsiveness of the channels to Ca2+. Physiologically, these K+ channels may contribute to the basolateral K+ conductance of the duct cell and, by providing a pathway for current flow across the basolateral membrane, play an important role in pancreatic bicarbonate secretion. |
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Keywords: | pancreatic duct cells bicarbonate secretion patch clamp Ca2+-activated K+ channels protein kinase-A cyclic AMP-dependent phosphorylation |
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