Specific inhibition of stretch‐induced increase in L‐type calcium channel currents by herbimycin A in canine basilar arterial myocytes

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Abstract
The effects of protein‐tyrosine kinase (PTK) and protein‐tyrosine phosphatase (PTP) inhibitors on voltage‐activated barium currents (IBa) through L‐type calcium channels increased by hypotonic solution were investigated in canine basilar arterial myocytes by the whole‐cell patch‐clamp technique. IBa was elicited by depolarizing step from a holding potential of −80 to +10 mV and identified by using an L‐type calcium channel agonist, Bay K 8644 (100 nM), and an L‐type calcium channel blocker, nicardipine (1 μM). Hypotonic superfusate induced cell swelling and acted as a stretch stimulus, which reversibly increased peak IBa amplitude at +10 mV. IBa was also decreased by nicardipine (1 μM) under the hypotonic condition. PTK inhibitors such as herbimycin A (30 nM), genistein (10 μM), and lavendustin A (10 μM) decreased IBa enhanced by hypotonic solution. Genistein also decreased IBa in a concentration‐dependent manner under the isotonic condition. The inactive genistein analogue daidzein (10 μM) had no effect on IBa under either the isotonic or hypotonic condition. By contrast, herbimycin A did not decrease IBa under the isotonic condition. Sodium orthovanadate (10 μM), a PTP inhibitor, increased IBa under both conditions. The present results suggest that cell swelling by hypotonic solution increases the L‐type calcium channel currents in canine basilar artery and that herbimycin‐sensitive PTK activity is primarily involved in the enhancement of calcium channel currents. British Journal of Pharmacology (2000) 130, 923–931; doi:10.1038/sj.bjp.0703360

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