Protein kinase c inhibits delayed rectifier potassium current in
rabbit vascular smooth muscle cells.
Aiello, Ernesto A., Odile Cl[acute]ement-Chomienne, David P. Sontag,
Michael P. Walsh, and William C. Cole.
Smooth Muscle Research Group, Faculty of Medicine, University of
Calgary, Calgary, Alberta, Canada
APStracts 2:0544H, 1995.
The effect of protein kinase C (PKC) activation on 4-aminopyridine
(4AP)-sensitive delayed rectifier current (IdK) was studied in
isolated rabbit portal vein smooth muscle cells using standard whole
-cell voltage clamp. The effects of the phorbol ester, 4[beta]
-phorbol-12,13-dibutyrate (PdBu, 100 nM) and diacylglycerol analogues,
1,2-dioctanoyl-sn-glycerol (1,2-diC8, 10 [mu]M) and 1,3-dioctanoyl
-sn-glycerol (1,3-diC8, 10 [mu]M), on macroscopic, whole-cell IdK were
assessed in myocytes dialysed with 10 mM 1,2-bis(2-aminophenoxy)
-ethane-N,N,N',N'-tetraacetic acid (BAPTA) and 5 mM adenosine 5'
-triphosphate (ATP) (20-22 C). Activation of PKC by 1,2-diC8 or PdBu
caused a decline in IdK which was reversed upon washout of drug. 1,2
-diC8 had no effect on outward current present after exposure to 4AP
(20 mM). The inactive analogue, 1,3-diC8, did not affect IdK, but
subsequent exposure to the active analogue, 1,2-diC8, caused a marked
depression of the current. The inhibition of IdK by 1,2-diC8 was
significantly reduced by intracellular dialysis with the inhibitors
of PKC, chelerythrine (50 [mu]M) and calphostin C (1 [mu]M).
Substitution of extracellular Ca2+ with Mg2+ in the presence of 10 mM
intracellular BAPTA did not affect the suppression of IdK by 1,2
-diC8, indicating the involvement of a Ca2+-independent isoform of
PKC. This study suggests a novel signal transduction mechanism for
inhibition of 4AP-sensitive IdK involving a phosphotransferase
reaction catalyzed by PKC in vascular smooth muscle myocytes.
Received 1 August 1995; accepted in final form 28 November 1995.
APS Manuscript Number H724-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95