Modulation of the inwardly rectifying K+ channel in isolated human atrial myocytes by alpha 1-adrenergic stimulation

The Journal of Membrane Biology
R Sato, S Koumi

Abstract

We have examined the alpha 1-adrenergic modulation of the inwardly-rectifying K+ channel (IK1) in isolated human atrial myocytes using the patch clamp technique. alpha 1-Adrenergic agonist methoxamine produced action potential prolongation and a depolarization of the resting membrane potential. Under whole-cell voltage-clamp conditions, bath application of methoxamine can inhibit macroscopic IK1. The methoxamine-induced inhibition was reversible and concentration dependent, with the concentration for half-maximal inhibition being 18 microM. The methoxamine-induced inhibition of IK1 was prevented by bath application of alpha 1-adrenergic blocker prazosin. The current was similarly inhibited by phorbol ester (PMA), an activator of protein kinase C (PKC). In contrast, methoxamine failed to inhibit the current in the presence of a specific PKC inhibitor H-9, suggesting that PKC is involved in the methoxamine-induced inhibition of IK1. In single channel recording from cell-attached patches, bath-applied methoxamine could suppress IK1 channels by decreasing the frequency and duration of bursting without affecting unitary amplitude. Direct application of purified PKC to excised inside-out patches inhibited channel activity similar to ...Continue Reading

Citations

Dec 5, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Antony J Workman
Aug 29, 2006·Medical & Biological Engineering & Computing·Teun P de BoerMarcel A G van der Heyden
Apr 26, 2014·Circulation Research·Peng-Sheng ChenStanley Nattel
Aug 16, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Peter MelnykStanley Nattel
Aug 14, 1999·Progress in Biophysics and Molecular Biology·Y Shimoni
Jan 16, 1998·Cellular Signalling·N Dascal

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