Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.
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 alpha and beta1 subunits. Here we show that targeted deletion of the gene for the beta1 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 beta1 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.
Brenner
R
R
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, California 94305, USA.
Peréz
G J
GJ
Bonev
A D
AD
Eckman
D M
DM
Kosek
J C
JC
Wiler
S W
SW
Patterson
A J
AJ
Nelson
M T
MT
Aldrich
R W
RW
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D020013:Calcium Signaling; D002536:Cerebral Arteries / Q000502:physiology; D005260:Female; D018390:Gene Targeting; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger