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J Appl Physiol 91: 1350-1354, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 3, 1350-1354, September 2001

beta 1-subunit of BK channels regulates arterial wall [Ca2+] and diameter in mouse cerebral arteries

Matthias Löhn, Birgit Lauterbach, Hermann Haller, Olaf Pongs, Friedrich C. Luft, and Maik Gollasch

Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Charité University Hospitals, Humboldt University of Berlin, D-13125 Berlin; Institut für Neuronale Signalverarbeitung, ZMNH, University of Hamburg, D-20246 Hamburg; and Department of Nephrology, Medical School Hannover, D-30625 Hannover, Germany

Mice with a disrupted beta 1 (BKbeta 1)-subunit of the large-conductance Ca2+-activated K+ (BK) channel gene develop systemic hypertension and cardiac hypertrophy, which is likely caused by uncoupling of Ca2+ sparks to BK channels in arterial smooth muscle cells. However, little is known about the physiological levels of global intracellular Ca2+ concentration ([Ca2+]i) and its regulation by Ca2+ sparks and BK channel subunits. We utilized a BKbeta 1 knockout C57BL/6 mouse model and studied the effects of inhibitors of ryanodine receptor and BK channels on the global [Ca2+]i and diameter of small cerebral arteries pressurized to 60 mmHg. Ryanodine (10 µM) or iberiotoxin (100 nM) increased [Ca2+]i by ~75 nM and constricted +/+ BKbeta 1 wild-type arteries (pressurized to 60 mmHg) with myogenic tone by ~10 µm. In contrast, ryanodine (10 µM) or iberiotoxin (100 nM) had no significant effect on [Ca2+]i and diameter of -/- BKbeta 1-pressurized (60 mmHg) arteries. These results are consistent with the idea that Ca2+ sparks in arterial smooth muscle cells limit myogenic tone through activation of BK channels. The activation of BK channels by Ca2+ sparks reduces the voltage-dependent Ca2+ influx and [Ca2+]i through tonic hyperpolarization. Deletion of BKbeta 1 disrupts this negative feedback mechanism, leading to increased arterial tone through an increase in global [Ca2+]i.

calcium; calcium-activated potassium channels; pressurized cerebral arteries; arterial tone; BKbeta 1 knockout mouse


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