This project will test the hypotheses that 1) G protein activates VSM L-type Ca2+ channels via cAMP/PK-A pathway, and 2) cGMP may exerts its inhibitory effect on these Ca2+ channels via phosphorylation of Ca2+ channels or some regulatory proteins by PKG. These hypotheses will be evaluated by utilizing freshly isolated portal vein myocytes, transiently expressed VSM L-type Ca2+ subunits, purified G protein subunits, and variety of non- specific and specific protein kinase blockers. Results from this project will provide cellular events by which G proteins and protein kinases regulate Ca2+ entry in VSM cells following physiological stimulation to induce vasodilation and vasoconstriction. Ca2+ channels are targets for a number of 2drugs used in the treatment of hypertension such as dihydropyridines, and adrenergic agonists and antagonists. By further defining the signal transduction pathways regulating Ca2+ entry, new strategies could be developed to control high blood pressure.
| Zhong, J; Hume, J R; Keef, K D (2001) beta-Adrenergic receptor stimulation of L-type Ca2+ channels in rabbit portal vein myocytes involves both alphas and betagamma G protein subunits. J Physiol 531:105-15 |
| Zhong, J; Hume, J R; Keef, K D (1999) Anchoring protein is required for cAMP-dependent stimulation of L-type Ca(2+) channels in rabbit portal vein. Am J Physiol 277:C840-4 |
