Inhibition of slow-wave repolarization and Ca(2+)-activated K+ channels by quaternary ammonium ions

A Carl1, B W Frey, S M Ward

  • 1Department of Physiology, University of Nevada School of Medicine, Reno 89557-0046.

Insights

Tetrapentylammonium (TPeA) prolongs colonic smooth muscle slow waves by blocking potassium channels. Intracellular TPeA is a potent blocker of large-conductance calcium-activated potassium (BK) channels, essential for repolarization.

Area of Science:

  • Physiology
  • Pharmacology
  • Ion Channel Biology

Background:

  • Potassium (K+) channels play a crucial role in regulating smooth muscle electrical activity.
  • Understanding K+ channel function is vital for elucidating mechanisms of gastrointestinal motility.

Purpose of the Study:

  • To investigate the effects of the K+ channel blocker tetrapentylammonium (TPeA) on canine colonic smooth muscle electrical activity.
  • To characterize the block of large-conductance calcium-activated potassium (BK) channels by TPeA and tetraethylammonium (TEA) using the patch-clamp technique.

Main Methods:

  • Studied intact circular smooth muscle from canine colon.
  • Utilized the patch-clamp technique on excised and cell-attached patches from isolated colonic smooth muscle cells.
  • Characterized voltage-dependent binding kinetics of TPeA and TEA to BK channels.

Main Results:

  • TPeA (10 and 20 microM) increased slow-wave duration and plateau potential, indicating K+ channels are essential for terminating colonic slow waves.
  • Intracellular TPeA was a potent blocker of BK channel current (Kd(0) = 11.7 microM) with significant voltage dependence.
  • TPeA also blocked other K+ channels, including 70-pS and 23-pS channels.

Conclusions:

  • K+ channels are critical for the repolarization phase of colonic smooth muscle slow waves.
  • TPeA effectively blocks BK channels, particularly from the intracellular side, impacting colonic electrical activity.
  • TPeA serves as a valuable tool for studying K+ channel function in smooth muscle physiology.

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