title: Cross talk between plasma membrane Na(+)/Ca (2+) exchanger-1 and TRPC/Orai-containing channels: key players in arterial hypertension.
abstract: Arterial smooth muscle (ASM) Na(+)/Ca(2+) exchanger type 1 (NCX1) and TRPC/Orai-containing receptor/store-operated cation channels (ROC/SOC) are clustered with α2 Na(+) pumps in plasma membrane microdomains adjacent to the underlying junctional sarcoplasmic reticulum. This arrangement enables these transport proteins to function as integrated units to help regulate local Na(+) metabolism, Ca(2+) signaling, and arterial tone. They thus influence vascular resistance and blood pressure (BP). For instance, upregulation of NCX1 and TRPC6 has been implicated in the pathogenesis of high BP in several models of essential hypertension. The models include ouabain-induced hypertensive rats, Milan hypertensive rats, and Dahl salt-sensitive hypertensive rats, all of which exhibit elevated plasma ouabain levels. We suggest that these molecular mechanisms are key contributors to the increased vascular resistance ("whole body autoregulation") that elevates BP in essential hypertension. Enhanced expression and function of ASM NCX1 and TRPC/Orai1-containing channels in hypertension implies that these proteins are potential targets for pharmacological intervention.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Pulina
authors.forename: A
authors.initials: A
authors.lastname: Zulian
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Baryshnikov
authors.forename: Cristina I
authors.initials: CI
authors.lastname: Linde
authors.forename: Eiji
authors.initials: E
authors.lastname: Karashima
authors.forename: John M
authors.initials: JM
authors.lastname: Hamlyn
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferrari
authors.forename: Mordecai P
authors.initials: MP
authors.lastname: Blaustein
authors.forename: Vera A
authors.initials: VA
authors.lastname: Golovina
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D020303:Rats, Inbred Dahl; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel
chemical_list: D009124:Muscle Proteins; D019831:Sodium-Calcium Exchanger; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C492145:Trpc6 protein, rat; C110374:sodium-calcium exchanger 1; D012964:Sodium; D002118:Calcium