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Stimulation of the BKCa channel in cultured smooth muscle cells of human trachea by magnolol

Abstract

Background: Magnolol, a compound isolated from the cortex of Magnolia officinalis, has been found to possess anti-allergic and anti-asthmatic activity.

Methods: The effect of magnolol on ionic currents was studied in cultured smooth muscle cells of human trachea with the aid of the patch clamp technique.

Results: In whole cell current recordings magnolol reversibly increased the amplitude of K+ outward currents. The increase in outward current caused by magnolol was sensitive to inhibition by iberiotoxin (200 nM) or paxilline (1 μM) but not by glibenclamide (10 μM). In inside out patches, magnolol added to the bath did not modify single channel conductance but effectively enhanced the activity of large conductance Ca2+ activated K+ (BKCa) channels. Magnolol increased the probability of these channel openings in a concentration dependent manner with an EC50 value of 1.5 μM. The magnolol stimulated increase in the probability of channels opening was independent of internal Ca2+. The application of magnolol also shifted the activation curve of BKCa channels to less positive membrane potentials. The change in the kinetic behaviour of BKCa channels caused by magnolol in these cells is the result of an increase in dissociation and gating constants.

Conclusions: These results provide evidence that, in addition to the presence of antioxidative activity, magnolol is potent in stimulating BKCa channel activity in tracheal smooth muscle cells. The direct stimulation of these BKCa channels by magnolol may contribute to the underlying mechanism by which it acts as an anti-asthmatic compound.

  • magnolol
  • Ca2+ activated K+ current
  • large conductance Ca2+ activated K+ channel
  • human tracheal smooth muscle cells

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