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(Circulation Research. 2000;86:717.)
© 2000 American Heart Association, Inc.

Editorial

Connections Count

Excitation-Contraction Meets Excitation-Transcription Coupling

Mark E. Anderson

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

Correspondence to Mark E. Anderson, MD, PhD, Vanderbilt University Medical Center, Departments of Medicine and Pharmacology, 315 Medical Research Building II, Nashville, TN 37232-6300. E-mail mark.anderson@mcmail.vanderbilt.edu

Key Words: L-type Ca²⁺ channel • [Ca²⁺]_i • nuclear pore • calmodulin kinase • adenylate cyclase

	Introduction

 
It is increasingly clear that cell-signaling systems serve multiple functions. Signaling molecules that play a highly visible functional role in muscle by regulating intracellular Ca²⁺ ([Ca²⁺]_i) homeostasis and contraction are also coupled to the genetic machinery of the cell and thereby shape the repertoire of expressed proteins. Our emerging understanding of excitation-contraction coupling (ECC) follows this theme (Figure). ECC occurs when Ca²⁺ entry, mostly through L-type Ca²⁺ channels,^{1 2} activates Ca²⁺ release from channels guarding the content of [Ca²⁺]_i stores. In vascular smooth muscle, 2 channel types are important: ryanodine receptors that operate by a Ca²⁺-induced Ca²⁺ release mechanism³ and inositol trisphosphate (IP₃) receptors that are sensitized by [Ca²⁺]_i but open after binding IP₃.⁴ The situation in cardiomyocytes seems to be somewhat simpler, as only the ryanodine receptors have a demonstrated role in ECC. ECC is mainly controlled by short-term signaling events to regulate the continuous ebb and flow of activator [Ca²⁺]_i that is necessary for cycling myofilament crossbridge formation. Nevertheless, the molecular machinery of ECC also regulates the transcriptional activity of the cell over a much longer time scale by a process termed excitation-transcription coupling (ETC).⁵

View larger version (24K): [in this window] [in a new window]   Figure 1. Interaction of ECC (solid arrows) and ECT (dashed arrows) may occur at different levels within the cell. The cell membrane (1) is the site of proteins, such as the voltage-gated L-type Ca2+ channel, that govern Ca2+ entry into the cell. Ca2+ entry is further regulated at the cell membrane by other Ca2+-activated ion channels . . . [Full Text of this Article]

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