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(Circulation Research. 2006;98:979.)
© 2006 American Heart Association, Inc.

Editorials

A New Role for Calmodulin in Ion Channel Biology

Dan M. Roden

From the Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Dan M. Roden, MD, Professor of Medicine and Pharmacology, Director, Oates Institute for Experimental Therapeutics, Assistant Vice-Chancellor for Personalized Medicine, Vanderbilt University School of Medicine, 1285 Medical Research Building IV, Nashville, TN 37232. E-mail dan.roden@vanderbilt.edu

See related articles, pages 1048–1054 and 1055–1063

Key Words: calmodulin • potassium channel • trafficking • processing • calcium

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

	Delayed Rectifier Currents in Heart

 
A time-dependent repolarizing current carried by outward movement of potassium ions was first identified by Hodgkin and Huxley, and has been recognized in heart since the 1960s.^1,2 Experiments in the 1980s found that the amplitude of the current, then termed I_K, increased when intracellular calcium was increased.³ The key advance to further understanding of the physiology of this important repolarizing current was the recognition in 1990 that it includes at least two distinct components, now termed I_Kr and I_Ks.⁴ These two currents have very different voltage-dependent gating behaviors and sensitivities to drugs and to activation of second messenger pathways. The amplitude and gating of I_Ks is quite labile in experimental preparations and increases dramatically in response to activation of PKA.^5–7 Such I_Ks variability has been invoked as a mechanism underlying variability in the extent to which I_Kr blockers prolong QT interval, a common problem in clinical medicine and drug development.^7–10 At its simplest level, patients with robust I_Ks display minimal QT prolongation with I_Kr block, whereas those with I_Ks reduction may display little QT prolongation at baseline but striking QT prolongation when I_Kr, the major mechanism supporting normal repolarization in this setting, is blocked by drugs.

Molecular genetic studies in the mid 1990s led to identification of the genes whose expression underlies these currents: I_Kr is generated by expression of KCNH2 (initially termed HERG), and I_Ks is generated by the coexpression of a pore forming subunit, KCNQ1 (formerly termed KvLQT1), with important function modifying ancillary . . . [Full Text of this Article]

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Circ. Res. 2006 98: 1048-1054. [Abstract] [Full Text] [PDF]

Calmodulin Is Essential for Cardiac I_KS Channel Gating and Assembly: Impaired Function in Long-QT Mutations

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				M. Bal, O. Zaika, P. Martin, and M. S. Shapiro Calmodulin binding to M-type K+ channels assayed by TIRF/FRET in living cells J. Physiol., May 1, 2008; 586(9): 2307 - 2320. [Abstract] [Full Text] [PDF]