BASIC FGF ENHANCES CALCIUM-PERMEABLE CHANNEL OPENINGS IN ADULT-RAT CARDIAC MYOCYTES - IMPLICATION IN THE BFGF-INDUCED INCREASE OF FREE CA2+CONTENT

Basic fibroblast growth factor (bFGF) has been implicated in the chang es in gene expression that, under pathological conditions such as isch emia or volume overload, lead to adult cardiomyocyte hypertrophy. In m any tissues, one of the first events following cell activation by grow th factors is an enhancement of the intracellular free calcium concent ration, generated by fluxes from internal storage compartments and thr ough channels of the plasma membrane. The present study was undertaken to determine whether cardiac myocytes isolated from adult rat ventric les express Ca2+-permeable channels activated by bFGF. Using the cell- attached mode of the patch-clamp technique, we observed that bFGF (fro m 0.1-10 nM) induced an increase of fast burst openings, mediated by C a2+-permeable channels with low conductance (15 pS) and voltage-indepe ndence. Inside-out patch-clamp experiments revealed that inositol 1,4, 5-trisphosphate (5 mu M) enhanced the opening of Ca2+-permeable channe ls with similar properties as the bFGF-induced channels, indicating th at IP3 may be a second messenger of this process. Confocal fluorescenc e imaging of intracellular free calcium provided direct evidence that bFGF induced an increase of cytoplasmic and nucleoplasmic free Ca2+ co ncentrations which were generated, in part, by Ca2+ influx through the plasma membrane. In conclusion, this study supports the presence, in the plasma membrane of adult cardiac myocytes, of messenger-activated calcium channels which could play key roles in the calcium-dependent p athways that are activated in response to growth factors. (C) 1997 Aca demic Press Limited.