G-proteins and transmembrane signalling

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The co-ordinated regulation of cellular functions by hormones is vital to be able to respond to both immediate and long-term environmental changes and stresses. The stress hormone, adrenaline, affects in particular, the cardiovascular system, causing constriction of small arteries and increases in the force and rate of contraction of the heart, by binding to, and activating, adrenergic receptor proteins present on the cell surface. Activation of these receptors is implicated in the development of cardiac hypertrophy, as well as ventricular arrhthymias following ischaemia and reperfusion. Understanding the precise mechanisms or pathways of activation of these receptors is, therefore, of direct relevance to the treatment of these important clinical disorders. We have recently discovered a new protein, Gh, involved in the regulation of cellular functions by adrenergic receptors. The aims of this proposal are to determine the importance of Gh in the heart and understand the molecular mechanisms that control the function of this protein. Such insights are of paramount importance as they have direct applicability to our understanding of the heart s response to stress and may lead to new diagnostic or therapeutic approaches for the treatment of cardiac diseases.