Expression of Multiple Splice Variant Forms of RGS6 in Mouse Ventricular Myocytes

Expression of Multiple Splice Variant Forms of RGS6 in Mouse Ventricular Myocytes GPCR signaling in cardiac myocytes is essential for normal cardiovascular function. RGS proteins are key regulators of GPCR signaling due to their GAP activity toward G proteins. Recent studies have shown an essential role of RGS proteins in regulating chronotropic responses in mice, although the identity of the RGS proteins involved is unknown. RGS6 is one of three RGS genes expressed highly in atrial and ventricular cardiac myocytes (VCM). We undertook studies to determine whether RGS6 exists in multiple splice forms in VCM, in view of our evidence for the existence of thirty‐six human RGS6 splice forms. RGS6 immunoreactivity in VCM lysates co‐migrates with the DEP domain‐containing RGS6L splice forms. Nine C‐terminal forms of RGS6L exist in humans and each contains a complete or incomplete GGL domain. We amplified and cloned RGS6Lα2, a major RGS6L form in most tissues, from VCM and found it to be 98.7% identical to the human form. Using primers based upon mouse genomic sequence data, PCR was performed to determine which RGS6L C‐terminal splice forms are expressed in VCM. VCM express transcripts encoding each of the RGS6L C‐terminal splice forms, designated α1, α2, β1, β2, γ, δ, ε η and ζ. Notably, PCR products corresponding to the‐GGL forms of these transcripts are also present in VCM. Thus, VCM express multiple splice forms of RGS6L which may possess distinct roles in GPCR signaling in heart.