Subcellular compartmentalization of gs[alpha] in cardiac myocytes
and its redistribution in heart failure.
Nash, John A., H. Kirk Hammond, Jeffrey E. Saffitz.
Departments of Pathology and Medicine, Washington University, St.
Louis, MO 63110 and Department of Medicine, VAMC-San Diego and UCSD,
La Jolla, CA 92161
APStracts 3:0197H, 1996.
Intracellular compartmentalization of G proteins may contribute to
regulating signal transduction pathways in normal and failing
myocardium. To test this hypothesis, we used post-embedment
immunogold electron microscopy to characterize the subcellular
distribution of Gs[alpha] in normal canine and porcine left
ventricular myocytes and in myocytes from a pacing-induced heart
failure model in pigs in which [beta]-adrenergic signalling is
impaired. Gs[alpha] was highly compartmentalized in normal canine
myocytes and was localized specifically to the sarcolemma,
intercalated disks, T-tubule and sarcoplasmic reticulum (SR) triads,
and myoplasm. The highest Gs[alpha] concentration was observed in the
intercalated disks. Only 20+/-5% of total cellular Gs[alpha] was
localized to the sarcolemma. The triads and myoplasm compartments
contained 45+/-13% and 27+/-8% of total cellular Gs[alpha],
respectively. The distribution of Gs[alpha] in normal porcine and
canine myocytes was similar. However, in failing porcine myocytes
Gs[alpha] was redistributed from the sarcolemma and T-tubule/SR
triads to the myoplasm. The proportion of total cellular Gs[alpha] in
the sarcolemma fell from 22+/-5% in normal to 11+/-4% in failing
myocytes (p<.005), and the proportion in T-tubule/SR triads fell
from 55+/-5% to 40+/-5% (p<.01), with a quantitatively
corresponding increase in the proportion in the myoplasm from 19+/-3%
to 43+/-4% (p<.0001). Thus, redistribution of Gs[alpha] from the
sarcolemma and the T-tubule/SR triads, where it may transduce [beta]
-adrenergic signals, to internal sites where such actions may be
precluded, might contribute to the pathophysiology of heart failure.
Received 21 December 1995; accepted in final form 16 April 1996.
APS Manuscript Number H1188-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96