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Biomedical Imaging Group, Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01655

Address correspondence to John V. Walsh, Jr, Department of Physiology, University of Massachusetts Medical Center, Worcester, MA 01655. Fax: (508) 856-5997; E-mail: john.walsh{at}umassmed.edu

Ca²⁺ sparks are small, localized cytosolic Ca²⁺ transients due to Ca²⁺ release from sarcoplasmic reticulum through ryanodine receptors. In smooth muscle, Ca²⁺ sparks activate large conductance Ca²⁺-activated K⁺ channels (BK channels) in the spark microdomain, thus generating spontaneous transient outward currents (STOCs). The purpose of the present study is to determine experimentally the level of Ca²⁺ to which the BK channels are exposed during a spark. Using tight seal, whole-cell recording, we have analyzed the voltage-dependence of the STOC conductance (g_(STOC)), and compared it to the voltage-dependence of BK channel activation in excised patches in the presence of different [Ca²⁺]s. The Ca²⁺ sparks did not change in amplitude over the range of potentials of interest. In contrast, the magnitude of g_(STOC) remained roughly constant from 20 to -40 mV and then declined steeply at more negative potentials. From this and the voltage dependence of BK channel activation, we conclude that the BK channels underlying STOCs are exposed to a mean [Ca²⁺] on the order of 10 µM during a Ca²⁺ spark. The membrane area over which a concentration 10 µM is reached has an estimated radius of 150–300 nm, corresponding to an area which is a fraction of one square micron. Moreover, given the constraints imposed by the estimated channel density and the Ca²⁺ current during a spark, the BK channels do not appear to be uniformly distributed over the membrane but instead are found at higher density at the spark site.

Key Words: calcium signaling • ion channel • STOC • sarcoplasmic reticulum • smooth muscle

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