Carbachol induces sustained glucose-dependent oscillations of cytoplasmic Ca2+ in hyperpolarized pancreatic beta cells.
The effect of carbachol on the cytoplasmic Ca2+ concentration [( Ca2+]i) was studied in insulin-releasing mouse pancreatic beta cells hyperpolarized by the K(+)-channel-activating agent diazoxide. By mobilizing intracellular Ca2+, carbachol induced an initial [Ca2+]i transient, which was more than tenfold higher after preexposure to 20 mM glucose than in a medium lacking substrate. The transient was followed by a sustained but less pronounced elevation, probably due to activation of the potential-independent entry of Ca2+. In individual beta cells exposed to 20 mM glucose small oscillations with a frequency of 1-4/min were superimposed on the sustained phase. These oscillations were insensitive to methoxyverapamil, and their frequency increased in a Na(+)-deficient medium. However, the oscillations faded away after lowering glucose to 3 mM and reappeared when increasing the sugar concentration. The results indicate that the glucose concentration is an important permissive determinant for sustained oscillations of [Ca2+]i in response to agents stimulating the formation of inositol 1,4,5-trisphosphate.
Gylfe
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Department of Medical Cell Biology, Uppsala University, Sweden.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice
D005711:Gallopamil; D002217:Carbachol; D005947:Glucose; D003981:Diazoxide; D002118:Calcium