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(Circulation Research. 2006;98:860.)
© 2006 American Heart Association, Inc.

Editorials

Serotonin-Induced Inhibition of K_V Current

A Supporting Role in Pulmonary Vasoconstriction?

Anthony Varghese, Zhigang Hong, Edward Kenneth Weir

From the Division of Cardiology (K.E.W.), Veterans Affairs Medical Center, Minneapolis, and the Department of Medicine (A.V., Z.H., K.E.W.), University of Minnesota, Minneapolis.

Correspondence to E.K. Weir, MD, Cardiology (111 C), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417. E-mail weirx002@umn.edu

See related article, pages 931–938

Key Words: serotonin • potassium channels • pulmonary hypertension

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Pulmonary vascular tone is largely determined by potassium and calcium currents in the smooth muscle cells (SMCs) of the small resistance arteries. Under normoxic circumstances an outward potassium current (I_K) passes through voltage-gated (K_v), calcium-activated (K_Ca), and background tandem-pore domain (K_2P) potassium channels. The latter (coded by the KCNK family of genes) include the twik-related acid sensitive K⁺ channel TASK and TASK-like channels. This current keeps the resting membrane potential in the range of –50 to –60 mV and inhibits calcium entry through L-type calcium channels.¹ Vasodilator substances such as nitric oxide and prostacyclin, released from the endothelium, increase I_K, one of several actions that lead to further vasodilatation.^2,3 Vasoconstrictor substances, such as endothelin, can inhibit I_K⁴ and/or release calcium from the sarcoplasmic reticulum.⁵ In addition to vasoactive effects, an increase in cytosolic potassium inhibits smooth muscle cell apoptosis,⁶ and an increase in cytosolic calcium promotes cellular proliferation.⁷ Consequently, the inhibition of I_K is important not only in causing membrane depolarization and calcium entry but also in stimulating vascular remodeling and in the development of chronic pulmonary hypertension. Agents that can cause pulmonary hypertension, such as the anorectic drugs and hypoxia, inhibit I_K^8,9 and also enhance calcium release from the sarcoplasmic reticulum, leading to subsequent repletion of calcium through store-operated channels.^10,11,12 The smooth muscle cells in the resistance pulmonary arteries of patients with pulmonary arterial hypertension (PAH) exhibit both reduced I_K and decreased expression of K_v channels,¹³ and also increased expression of the TRPC . . . [Full Text of this Article]

Related Article:

Serotonin Inhibits Voltage-Gated K⁺ Currents in Pulmonary Artery Smooth Muscle Cells: Role of 5-HT_2A Receptors, Caveolin-1, and K_V1.5 Channel Internalization

Angel Cogolludo, Laura Moreno, Federica Lodi, Giovanna Frazziano, Laura Cobeño, Juan Tamargo, and Francisco Perez-Vizcaino
Circ. Res. 2006 98: 931-938. [Abstract] [Full Text] [PDF]