KCa channel insensitivity to Ca sparks underlies fractional uncoupling in newborn cerebral artery smooth muscle cells

Li, Anlong, Adebowale Adebiyi, Charles W. Leffler, and Jonathan H. Jaggar. KCa channel insensitivity to Ca sparks underlies fractional uncoupling in newborn cerebral artery smooth muscle cells. Am J Physiol Heart Circ Physiol 291: H1118–H1125, 2006. First published April 7, 2006; doi:10.1152/ajpheart.01308.2005.—In smooth muscle cells, localized intracellular Ca transients, termed “Ca sparks,” activate several large-conductance Ca -activated K (KCa) channels, resulting in a transient KCa current. In some smooth muscle cell types, a significant proportion of Ca sparks do not activate KCa channels. The goal of this study was to explore mechanisms that underlie fractional Ca spark-KCa channel coupling. We investigated whether membrane depolarization or ryanodine-sensitive Ca release (RyR) channel activation modulates coupling in newborn (1to 3-day-old) porcine cerebral artery myocytes. At steady membrane potentials of 40, 0, and 40 mV, mean transient KCa current frequency was 0.18, 0.43, and 0.26 Hz and KCa channel activity [number of KCa channels activated by Ca sparks open probability of KCa channels at peak of Ca sparks (NPo)] at the transient KCa current peak was 4, 12, and 24, respectively. Depolarization between 40 and 40 mV increased KCa channel sensitivity to Ca sparks and elevated the percentage of Ca sparks that activated a transient KCa current from 59 to 86%. In a Ca -free bath solution or in diltiazem, a voltage-dependent Ca channel blocker, steady membrane depolarization between 40 and 40 mV increased transient KCa current frequency up to 1.6-fold. In contrast, caffeine (10 M), an RyR channel activator, increased mean transient KCa current frequency but did not alter Ca spark-KCa channel coupling. These data indicate that coupling is increased by mechanisms that elevate KCa channel sensitivity to Ca sparks, but not by RyR channel activation. Overall, KCa channel insensitivity to Ca sparks is a prominent factor underlying fractional Ca spark uncoupling in newborn cerebral artery myocytes.