REVIEW: Cation–Chloride Cotransporters: Regulation, Physiological Significance, and Role in Pathogenesis of Arterial Hypertension

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S. N. Orlov^1,2*, S. V. Koltsova¹, L. V. Kapilevich^2,3, N. O. Dulin⁴, and S. V. Gusakova³

¹Faculty of Biology, Lomonosov Moscow State University, Vorob’evy Gory 1/2, 119991 Moscow, Russia; E-mail: sergeinorlov@yandex.ru

²Tomsk State University, pr. Lenina 36, 634050 Tomsk, Russia

³Siberian State Medical University, Moskovskii Trakt 2, 634050 Tomsk, Russia

⁴University of Chicago, Chicago, 600637 IL, USA

^* To whom correspondence should be addressed.

Received July 23, 2014

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This review summarizes the data on the functioning of carriers providing electroneutral symport of sodium, potassium, and chloride (Na⁺,K⁺,2Cl^– cotransport), potassium and chloride (K⁺,Cl^– cotransport), and sodium and chloride (K⁺,Cl^– cotransport) as well as molecular mechanisms of the regulation of these carriers and their physiological significance. We emphasized the involvement of chloride-coupled carriers in the regulation of cell volume and intracellular chloride concentration and novel data on the role of ubiquitous isoform of Na⁺,K⁺,2Cl^– cotransporter NKCC1 in regulation of vascular smooth muscle contraction and activity of GABA_A receptors. Finally, we analyzed the data on activation of NKCC1 in patients with essential hypertension and its role in the long-term maintenance of elevated systemic blood pressure and myogenic response in microcirculatory beds.

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KEY WORDS: sodium, potassium, chloride, cotransport, smooth muscle, contraction, myogenic tone, sympathetic nervous system, hypertension

DOI: 10.1134/S0006297914130070

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