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

S. N. Orlov1,2*, S. V. Koltsova1, L. V. Kapilevich2,3, 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
This review summarizes the data on the functioning of carriers providing electroneutral symport of sodium, potassium, and chloride (Na+,K+,2Clcotransport), potassium and chloride (K+,Clcotransport), and sodium and chloride (K+,Clcotransport) 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+,2Clcotransporter NKCC1 in regulation of vascular smooth muscle contraction and activity of GABAA 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.
KEY WORDS: sodium, potassium, chloride, cotransport, smooth muscle, contraction, myogenic tone, sympathetic nervous system, hypertension

DOI: 10.1134/S0006297914130070