Gq‐initiated cardiomyocyte hypertrophy is mediated by phospholipase Cβ1b

Activation of the heterotrimeric G protein Gq causes cardiomyocyte hypertrophy in vivo and in cell culture models. Hypertrophic responses induced by pressure or volume overload are exacerbated by increased Gq activity and ameliorated by Gq inhibition. Gq activates phospholipase Cβ (PLCβ) subtypes, resulting in generation of the intracellular messengers inositol(1,4,5) tris ‐phosphate [Ins(1,4,5)P 3 ] and sn‐1,2‐diacylglycerol (DAG), which regulate intracellular Ca 2+ and conventional protein kinase C subtypes, respectively. Gq can also signal independently of PLCβ, and the involvement of either Ins(1,4,5)P 3 or DAG in cardiomyocyte hypertrophy has not been unequivocally established. Overexpression of one splice variant of PLCβ1, specifically PLCβ1b, in neonatal rat cardiomyocytes causes increased cell size, elevated protein/ DNA ratio, and heightened expression of the hypertrophy‐related marker gene, atrial natriuretic peptide. The other splice variant, PLCβ1a, had no effect. Expression of a 32‐aa C‐terminal PLCβ1b peptide, which competes with PLCβ1b for sarcolemmal association, prevented PLC activation and eliminated hypertrophic responses initiated by Gq or Gq‐coupled α 1 ‐adrenergic receptors. In contrast, a PLCβ1a C‐terminal peptide altered neither PLC activity nor cellular hypertrophy. We conclude that hypertrophic responses initiated by Gq are mediated specifically by PLCβ1b. Preventing PLCβ1b association with the sarcolemma may provide a useful therapeutic target to limit hypertrophy.—Filtz, T. M., Grubb, D. R., McLeod‐Dryden, T. J., Luo, J., Woodcock, E. A. Gq‐initiated cardiomyocyte hypertrophy is mediated by phospholipase Cβ1b. FASEB J . 23, 3564–3570 (2009). www.fasebj.org