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

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H Yokoshiki1, T Seki, M Sunagawa

  • 1Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. yokoshkk@med.hokudai.ac.jp

Canadian Journal of Physiology and Pharmacology
|September 28, 2000
PubMed

Insights

Large-conductance Ca2+-activated K+ channels (BKCa) in rat mesenteric arteries are inhibited by tyrosine phosphatase inhibitors. This suggests tyrosine phosphatases regulate BKCa channel activity in vascular smooth muscle cells.

Area of Science:

  • Physiology
  • Biochemistry
  • Pharmacology

Background:

  • Large-conductance Ca2+-activated K+ channels (BKCa) play a crucial role in regulating vascular tone.
  • The precise mechanisms controlling BKCa channel activity in vascular smooth muscle cells are not fully understood.
  • Tyrosine phosphatases (Tyr-PPs) are implicated in various cellular signaling pathways.

Purpose of the Study:

  • To investigate the potential regulation of BKCa channels by Tyr-PPs in rat mesenteric artery myocytes.
  • To determine if inhibiting Tyr-PPs affects BKCa channel function.

Main Methods:

  • Single-channel currents of rat mesenteric artery myocytes were recorded using the open cell-attached patch technique.
  • The effects of two Tyr-PP inhibitors, sodium orthovanadate (Na3VO4) and dephostatin, on BKCa channel activity were assessed.

Main Results:

  • BKCa channels (236 pS) activated at +40 mV and pCa 6 were significantly inhibited by 1 mM Na3VO4 (-81+/-3%, n = 10; P < 0.005).
  • 100 microM dephostatin also strongly inhibited BKCa channels (-80+/-7%, n = 7; P < 0.05).

Conclusions:

  • BKCa channels in vascular smooth muscle cells are likely regulated by tyrosine phosphatase-dependent signaling pathways.
  • Inhibition of these Tyr-PP pathways can attenuate BKCa channel activity, suggesting a potential therapeutic target.

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