Small arteries exhibit tone, a partially contracted state that is an import
ant determinant of blood pressure. In arterial smooth muscle cells, intrace
llular calcium paradoxically controls both contraction and relaxation. The
mechanisms by which calcium can differentially regulate diverse physiologic
al responses within a single cell remain unresolved. Calcium-dependent rela
xation is mediated by local calcium release from the sarcoplasmic reticulum
. These 'calcium sparks' activate calcium-dependent potassium (BK) channels
comprised of alpha and beta 1 subunits. Here we show that targeted deletio
n of the gene for the beta 1 subunit leads to a decrease in the calcium sen
sitivity of BK channels, a reduction in functional coupling of calcium spar
ks to BK channel activation, and increases in arterial tone and blood press
ure. The beta 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.