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(Circulation Research. 2000;87:535.)
© 2000 American Heart Association, Inc.

Editorial

Tails of the L-Type Ca²⁺ Channel

To Sense Oxygen or Not

Atsuko Yatani, Timothy J. Kamp

From the Departments of Pharmacology and Cell Biophysics (A.Y.), University of Cincinnati College of Medicine, Cincinnati, Ohio; Departments of Medicine and Physiology (T.J.K.), University of Wisconsin, Madison, Wis.

Correspondence to Dr Atsuko Yatani, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575. E-mail yatania@uc.edu

Key Words: L-type Ca²⁺ channels • ₁ subunit • hypoxia • patch clamp • mutagenesis

	Introduction

 
Voltage-gated L-type Ca²⁺ channels are multisubunit membrane-spanning proteins that play a prominent role in a variety of Ca²⁺ dependent processes in cells including excitation-contraction coupling in muscle cells, excitation-secretion coupling in endocrine and neuronal cells, and gene regulation. The L-type Ca²⁺ channel is composed of a central pore-forming, voltage-sensing ₁ subunit and auxiliary subunits including ß, ₂/, and .¹ Multiple genes are known to encode a variety of isoforms for each subunit. Given their prominent role in the regulation of cellular processes, it is not surprising that these channels are subject to extensive regulation. A myriad of neurohumoral factors can modulate Ca²⁺ channel function via a variety of transmembrane receptors and signaling cascades.¹ The best-studied example is ß-adrenergic receptor–mediated stimulation of cardiac L-type Ca²⁺ channels by the cAMP/cAMP-dependent protein kinase pathway. Most of these regulatory pathways are thought to act by altering the phosphorylation status of the channel, although the molecular details of these putative phosphorylation events have not been fully resolved. But the story does not end with these channels responding only to traditional neurohormones. Recent studies have also revealed that the L-type Ca²⁺ channel can be modulated by hypoxia both in native vascular smooth muscle cells,² carotid body chemoreceptor cells,³ and in recombinant systems.⁴

How can acute hypoxia regulate channel activity? Changes in cellular metabolism resulting from hypoxia or ischemia can modulate channel function by changing the phosphorylation status of the channel. However, there are many other manners in which channels may respond more directly and rapidly to . . . [Full Text of this Article]