Involvement of the phospholipase C beta1 pathway in desensitization of the carbachol-activated nonselective cationic current in murine gastric myocytes

In murine gastrointestinal myocytes muscarinic stimulation activates nonselective cation channels via a G-protein and Ca2+-dependent pathway. We recorded inward cationic currents following application of carbachol (ICCh) to murine gastric myocytes held at -60 mV, using the whole-cell patch-clamp method. The properties of the inward cationic currents were similar to those of the nonselective cation channels activated by muscarinic stimulation in other gastrointestinal smooth muscle cells. CCh-induced ICCh and spontaneous decay of ICCh (desensitization of ICCh) occurred. Unlike the situation in guinea pig gastric myocytes, desensitization was not affected by varying EGTA]i. Pretreatment with the PLC inhibitor (U73122) blocked the activation of ICCh, and desensitization of ICCh was attenuated in PLC beta1 knock-out mice. These results suggest that the desensitization of ICCh in murine gastric myocytes is not due to a pathway dependent on intracellular Ca2+ but to the PLC beta1 pathway.