beta1 subunit of BK channels regulates arterial wall [Ca2+]i and diameter in mouse
cerebral arteries.
Löhn, Matthias, 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, Germany, D-13125 Berlin; Institut
für Neuronale Signalverarbeitung, ZMNH, University Hamburg, D-20246 Hamburg; and
Medical School Hannover, Department of Nephrology, D-30625 Hannover,
Germany
APStracts 8:0312A, 2001.
Mice with a disrupted beta1 (BKbeta1) 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 BKbeta1 knockout C57BL6 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 muM) or iberiotoxin (100 nM)
increased [Ca2+]i by ~75 nM and constricted +/+ BKbeta1 wild-type arteries
(pressurized to 60 mmHg) with myogenic tone by ~10 mum. In contrast, ryanodine (10
muM) or iberiotoxin (100 nM) had no significant effect on [Ca2+]i and diameter of
«minus»/«minus» BKbeta1-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 BKbeta1 disrupts this negative feedback mechanism, leading to increased
arterial tone through an increase in global [Ca2+]i.
Received 2 February 2001; accepted in final form 21 May 2001
APS Manuscript Number A0111-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001