Modulation of k channels by coexpressed human [alpha]1c
-adrenoceptor in xenopus oocytes.
Tseng, G. N., J. A. Yao, and J. Tseng-Crank.
Department of Pharmacology, Columbia University, New York, NY
10032, Wyeth-Ayerst Research, Princeton, NJ 08543-8000
APStracts 3:0347H, 1996.
[alpha]1-Adrenoceptors participate in the regulation of inotropy and
chronotropy in the heart. A modulation of cardiac K channel function
plays an important role in these [alpha]1-adrenergic functions.
Studies of the mechanisms of K channel modulation by [alpha]1
-adrenoceptors are hampered by the coexistence of multiple receptor
and channel subtypes in the heart. We therefore used a model system
of coexpressing a specific receptor (human [alpha]1C-adrenoceptor)
and a K channel clone (hIsK, rKv1.2 or rKv1.4) in oocytes. [alpha]1C
-adrenoceptor stimulation caused a rapid up-regulation of hIsK by
elevating [Ca]i. At least part of this effect was due to an
activation of calmodulin and Ca, calmodulin-dependent protein kinase
II. On the other hand, [alpha]1C-adrenoceptor stimulation caused a
slow down-regulation of rKv1.2 and rKv1.4 by activating PKC. The
differential modulation of K channels by [alpha]1C-adrenoceptors
demonstrated in our experiments corroborates the complexity of
[alpha]1-adrenergic functions in the heart. Our results indicate that
the oocyte model system can be a useful approach to studying
[alpha]1-adrenergic modulation of ion channel function and signal
transduction.
Received 19 December 1995; accepted in final form 7 August 1996.
APS Manuscript Number H1215-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996