Phorbol myristate acetate and ATP-sensitive potassium channels in insulin-secreting cells.
The actions of 4 beta-phorbol 12-myristate 13-acetate (PMA; 10-100 nM) on the ATP-sensitive K+ channel have been studied in the RINm5F insulin-secreting cell line. These experiments were carried out using the inside-out patch and open-cell recording configurations of the patch-clamp technique. In the presence of intracellular ATP and ADP, PMA was found to have complex effects. Over short periods of time, i.e., less than 5 min, PMA promoted channel inhibition. However, in the sustained presence of the phorbol ester, this inhibition was only transient and was followed by a period of recovery and then stimulation of the channels. There were no effects of PMA on ATP-sensitive K+ (K+ATP) channels in the absence of intracellular ATP/ADP and in patches of membrane excised from cells that had been pretreated overnight with 1 microM PMA to downregulate endogenous C-kinase. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate (10 nM-1 microM) was also found to have no actions on ATP-sensitive K+ channels. Overall, these data may suggest that through the modulation of protein kinase(s) associated with K+ATP channels, PMA is capable of causing both activation and inhibition of K+ channels in RINm5F cells.
Dunne
M J
MJ
Department of Biomedical Science, The University, Western Bank, Sheffield, United Kingdom.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002460:Cell Line; D004594:Electrophysiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D007328:Insulin; D015221:Potassium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate