RGS2 overexpression or G(i) inhibition rescues the impaired PKA signaling and slow AP firing of cultured adult rabbit pacemaker cells.

ABSTRACT: Freshly isolated adult rabbit sinoatrial node cells (f-SANC) are an excellent model for studies of autonomic signaling, but are not amenable to genetic manipulation. We have developed and characterized a stable cultured rabbit SANC (c-SANC) model that is suitable for genetic manipulation to probe mechanisms of spontaneous action potential (AP) firing. After 48 h in culture, c-SANC generate stable, rhythmic APs at 34±0.5°C, at a rate that is 50% less than f-SANC. In c- vs. f-SANC: AP duration is prolonged; phosphorylation of phospholamban at Ser(16) and type2 ryanodine receptor (RyR2) at Ser(2809) are reduced; and the level of type2 regulator of G-protein signaling (RGS2), that facilitates adenylyl cyclases/cAMP/protein kinase A (PKA) via G(i) inhibition, is substantially reduced. Consisten

SUBMITTER: Yang D 

PROVIDER: S-EPMC3472119 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature