1. Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA
2. Department of Pharmacology, College of Medicine, The University of Vermont, Burlington, Vermont 05405, USA
3. Department of Pathology, Palo Alto Veterans Administration Healthcare System, Palo Alto, California 94305 and Stanford University School of Medicine , Stanford, California 94305, USA
4. Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA

Correspondence to: Richard W. Aldrich¹ Correspondence and requests for materials should be addressed to R.W.A. (e-mail: Email: raldrich@leland.stanford.edu).

Abstract

Small arteries exhibit tone, a partially contracted state that is an important determinant of blood pressure. In arterial smooth muscle cells, intracellular calcium paradoxically controls both contraction and relaxation. The mechanisms by which calcium can differentially regulate diverse physiological responses within a single cell remain unresolved. Calcium-dependent relaxation is mediated by local calcium release from the sarcoplasmic reticulum. These 'calcium sparks' activate calcium-dependent potassium (BK) channels comprised of and 1 subunits. Here we show that targeted deletion of the gene for the 1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure. The 1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation.

1. Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA
2. Department of Pharmacology, College of Medicine, The University of Vermont, Burlington, Vermont 05405, USA
3. Department of Pathology, Palo Alto Veterans Administration Healthcare System, Palo Alto, California 94305 and Stanford University School of Medicine , Stanford, California 94305, USA
4. Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA

Correspondence to: Richard W. Aldrich¹ Correspondence and requests for materials should be addressed to R.W.A. (e-mail: Email: raldrich@leland.stanford.edu).