Inhibition of Ca2+-activated K+ channels by tyrosine phosphatase inhibitors in rat mesenteric artery

To investigate the possible regulation of large-conductance Ca2+-activated K+ channels (BKCa) by tyrosine phosphatases (Tyr-PPs), single-channel currents of myocytes from rat mesenteric artery were recorded in open cell-attached patches. Two structurally different Tyr-PP inhibitors, sodium orthovanadate (Na3VO4) and dephostatin, were used. The channels (236 pS) evoked at +40 mV and pCa 6, were significantly inhibited by 1 mM Na3VO4 (-81+/-3%, n = 10; P < 0.005). Similarly, 100 microM dephostatin strongly inhibited the BKCa channels (-80+/-7%, n = 7 ; P < 0.05). Therefore, BKCa channels in vascular smooth muscle cells may be regulated by tyrosine phosphatase-dependent signal transduction pathways, whose inhibition could attenuate the channel activity.