Identification of Canonical Transient Receptor Potential (TRPC) Channel Proteins in Native Vascular Smooth Muscle Cells

Anthony   P.   Albert; Sohag   N.   Saleh; William   A.   Large

Abstract

Canonical transient receptor potential (TRPC) channels are Ca2+-permeable non-selective cation channels, which on stimulation allow influx of Na+ and Ca2+ ions into cells. It is proposed that stimulation of TRPC conductances by neurotransmitters and hormones such as noradrenaline, angiotensin II and endothelin-1 have important functions in vascular smooth muscle cells including vasoconstriction, cell growth and proliferation. Moreover constitutive TRPC activity contributes to setting the resting membrane potential of vascular myocytes. Activation of TRPC channels is thought to provide a direct Ca2+ influx pathway and evoke indirect Ca2+ entry by inducing depolarisation and opening of voltagegated Ca2+ channels and by stimulating the reverse mode of the Na+/Ca2+ exchanger. Therefore identification of native TRPC channel proteins, which underlie these mechanisms, will provide important information on physiological functioning of vascular tissue and these conductances are pharmacological targets for the prevention of cardiovascular diseases such as hypertension. This review focuses on different experimental approaches that have been used to elucidate the molecular identity of TRPCs in native vascular myocytes. It will discuss the advantages and problems associated with using siRNA and antisense technologies in primary cell cultures, cell lines and transgenic mice models. In addition we describe recent work, which combines studies on the effect of anti-TRPC antibodies and pharmacological agents on biophysically characterised single cation channel currents to identify TRPC channel proteins in freshly dispersed vascular myocytes. These data provide strong evidence that native vascular myocytes contain diverse TRPC-mediated channels which are usually composed of complex heterotetrameric structures possessing marked pharmacological differences.

Keywords: Cation channels, vascular smooth muscle, canonical transient receptor potential, Ca2+ entry pathways

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