MEMBRANE DEPOLARIZATION COUPLESCa2+ SPARKS TO KCa CHANNELS IN NEWBORN ARTERIAL SMOOTH MUSCLE CELLS

In arterial smooth muscle cells, localized intracellular Ca 2+ transients, termed “Ca 2+ sparks”, activate several large‐conductance calcium‐activated potassium (K Ca ) channels, resulting in a transient K Ca current. In newborn porcine cerebral artery smooth muscle cells, a significant proportion of Ca 2+ sparks (~40 %) do not activate a transient K Ca current. The goal of this study was to investigate mechanisms that underlie sub‐unitary Ca 2+ spark to K Ca channel coupling in newborn (1–3 day old) porcine cerebral artery smooth muscle cells, and determine if ryanodine‐sensitive Ca 2+ release (RyR) channel activation or an elevation in K Ca channel Ca 2+ ‐sensitivity increase coupling. At steady membrane potentials of −40, 0 and +40 mV, mean transient K Ca current frequency was 0.18±0.02, 0.42±0.06, and 0.25±0.02 Hz, respectively. At the same potentials, Mean K Ca channel activity at the transient K Ca current peak (NP O ) was 4.2±0.3, 12.1±1.2 and 23.7±3.7, respectively. In diltiazem, a voltage‐dependent Ca 2+ channel blocker, depolarization between −40 and +40 mV increased mean transient K Ca current frequency 1.6–fold. Depolarization over the same voltage range also increased the percentage of Ca 2+ sparks that activated a transient K Ca current from 59±6 to 86±5%. Although caffeine (10uM), a RyR channel activator,increased mean transient K Ca current frequency by 1.5, 1.6 and 1.5‐fold at −40, 0 and +40 mV, respectively, caffeine did not alter the percentage of Ca 2+ sparks that activated transient K Ca current. Data indicate that K Ca channel Ca 2+ ‐sensitivity, as opposed to RyR channel activity, influences Ca 2+ spark to K Ca channel coupling in newborn arterial smooth muscle cells.