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.
Yokoshiki
H
H
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. yokoshkk@med.hokudai.ac.jp
Seki
T
T
Sunagawa
M
M
Sperelakis
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D015221:Potassium Channels; C084037:dephostatin; D014638:Vanadates; D017027:Protein Tyrosine Phosphatases; D002118:Calcium