Impaired Gsα and adenylyl cyclase cause β-adrenoceptor desensitization in chronically hypoxic rat hearts

Author:

Pei Jian-Ming1,Yu Xiao-Chun1,Fung Man-Lung12,Zhou Jing-Jun1,Cheung Chi-Sing1,Wong Nai-Sum3,Leung Maurrice-Ping42,Wong Tak-Ming12

Affiliation:

1. Departments of Physiology,

2. Institute of Cardiovascular Sciences and Medicine, Faculty of Medicine, University of Hong Kong, Hong Kong, China

3. Biochemistry, and

4. Pediatrics; and

Abstract

The effects of β-adrenoceptor stimulation with isoproterenol on electrically induced contraction and intracellular calcium ([Ca2+]i) transient, and cAMP in myocytes from both hypertrophied right and nonhypertrophied left ventricles of rats exposed to 10% oxygen for 4 wk, were significantly attenuated. The increased [Ca2+]i transient in response to cholera toxin was abolished, whereas increased cAMP after NaF significantly attenuated. The biologically active isoform, Gsα-small (45 kDa), was reduced while the biologically inactive isoform, Gsα-large (52 kDa), increased. The increased electrically induced [Ca2+]i transient and cAMP with 10–100 μM forskolin were significantly attenuated in chronically hypoxic rats. The content of Giα2, the predominant isoform of Gi protein in the heart, was unchanged. Results indicate that impaired functions of Gs protein and adenylyl cyclase cause β-adrenoceptor desensitization. The impaired function of the Gs protein may be due to reduced Gsα-small and/or increased Gsα-large, which does not result from changes in Gi protein. Responses to all treatments were the same for right and left ventricles, indicating that the impaired cardiac functions are not secondary to cardiac hypertrophy.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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