Spontaneous transient outward currents arise from microdomains where BK channels are exposed to a mean Ca2+ concentration on the order of 10 μM during a …

R ZhuGe, KE Fogarty, RA Tuft… - The Journal of general …, 2002 - rupress.org
R ZhuGe, KE Fogarty, RA Tuft, JV Walsh Jr
The Journal of general physiology, 2002rupress.org
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 …
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.
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