The muscarinic-gated k+ channel: subunit stoichiometry and
structural domains essential for g-protein stimulation.
Tucker, Stephen J., Mauro Pessia & John P. Adelman.
Vollum Institute for Advanced Biomedical Research, Oregon Health
Sciences University, Portland, Oregon, 97201 USA
APStracts 3:0197A, 1996.
Coexpression in Xenopus oocytes of the cloned cardiac inward rectifier
subunits Kir 3.1 and Kir 3.4 results in G-protein stimulated channel
activity closely resembling the muscarinic channel underlying IKAch
in atrial myocytes. To determine the stoichiometry and relative
subunit positions within the channel, Kir 3.1 and Kir 3.4 were
coexpressed in varying ratios with cloned G-b1g2 subunits, and also
as tandemly linked tetramers with different relative subunit
positions. The results reveal that the most efficient channel is
comprised of two subunits of each type in an alternating array within
the tetramer. To localize regions important for subunit coassembly
and G-protein sensitivity, chimeric subunits containing domains from
either Kir 3.1, Kir 3.4 or the G-protein insensitive subunit Kir 4.1
were expressed. The results demonstrate that the transmembrane
domains dictate the potentiation of the coassembled channels and that
although the N- or C-termini of both subunits alone can confer G
-protein sensitivity both termini are required for maximal stimulation
by G-b1g2.
Received 10 January 1996; accepted in final form 4 April 1996.
APS Manuscript Number A12-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96