Chapter

Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications

Volume 961 of the series Advances in Experimental Medicine and Biology pp 365-374

Date:

Cross Talk Between Plasma Membrane Na+/Ca2+ Exchanger-1 and TRPC/Orai-Containing Channels: Key Players in Arterial Hypertension

  • Maria V. PulinaAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , A. ZulianAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , Sergey G. BaryshnikovAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , Cristina I. LindeAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , Eiji KarashimaAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , John M. HamlynAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , Patrizia FerrariAffiliated withPrassis-sigma tau Research Institute
  • , Mordecai P. BlausteinAffiliated withDepartment of Physiology, University of Maryland School of Medicine
  • , Vera A. GolovinaAffiliated withDepartment of Physiology, University of Maryland School of Medicine Email author 

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Abstract

Arterial smooth muscle (ASM) Na+/Ca2+ 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, Ca2+ 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.

Keywords

Arterial smooth muscle cells Ca2+ signaling Store-operated channels Receptor-operated channels TRPC6 Ouabain-induced hypertensive rats Milan hypertensive strain rats Dahl salt-sensitive hypertensive rats