ABSTRACT
Calcium sparks are local transient elevations of intracellular calcium caused by the opening of ryanodine-sensitive, calcium-release channels (“ryanodine receptors”) in the sarcoplasmic reticulum membrane. In pressurized arteries, calcium sparks in smooth muscle cells occur at a frequency of about 1 per cell per second. This frequency depends on calcium entry through voltage-dependent calcium channels, and increases with pressure-induced depolarization and decreases with voltage-dependent calcium channel inhibition. Calcium sparks in pressurized arteries, even at the highest observed frequency, contribute little to overall average (“global”) intracellular calcium. Calcium sparks activate large-conductance, calcium-sensitive potassium (BKCa) channels in the surface membrane to cause a transient membrane potential hyperpolarization. Simultaneous measurements of calcium sparks and BKCa currents indicate that virtually every calcium spark increases the activity of about 20 nearby BKCa channels 10
6-fold. Disabling the communication of calcium sparks to BKCa channels by deleting the 1-subunit of the BKCa channel leads to depolarization and constriction of pressurized arteries, as well as to an elevation in blood pressure. These results support the concept that an elementary calcium signal (calcium spark) can regulate a global smooth muscle cell parameter (membrane potential) by providing high local calcium to BKCa channels, and that detuning this local communication, for example, 1 gene deletion, can elevate vascular tone and blood pressure.
