Sarcoplasmic reticulum calcium load regulates rat arterial smooth muscle calcium sparks and transient KCa currents

The regulation of calcium (Ca2+) sparks and transient calcium-sensitive K+ (K-Ca) currents by acute changes in sarcoplasmic reticulum (SR) Ca2+ load ([Ca2+](SR)) was investigated in rat cerebral artery smooth muscle cells using laser-scanning confocal microscopy in combination with patch clamp electrophysiology. [Ca2+](SR) was elevated by: (i) increasing the activity of the SR Ca2+-ATPase with an anti-phospholamban monoclonal antibody, or (ii) blocking Ca2+ release from the SR with tetracaine, a membrane-permeant, reversible ryanodine-sensitive Ca2+ release (RyR) channel blocker. Alternatively, [Ca2+](SR) was progressively decreased over time with a low concentration of thapsigargin (20 nm), a SR Ca2+-ATPase blocker. An elevation in [Ca2+] SR increased Ca2+ spark and transient K-Ca current frequency, but did not alter the amplitude, decay or spatial spread of Ca2+ sparks or the coupling ratio or amplitude correlation between Ca2+ sparks and evoked transient K-Ca currents. Decreasing [Ca2+](SR) reduced Ca2+ Spark frequency, amplitude and spatial spread and this reduced transient K-Ca current frequency and amplitude. However, even when mean Ca2+ spark amplitude and spread decreased by up to 47 and 56 % of control, respectively, the coupling ratio or amplitude correlation between Ca2+ sparks and transient K-Ca currents was not affected. These data demonstrate that acute changes in [Ca2+](SR) regulate Ca2+ sparks and transient K-Ca currents in arterial smooth muscle cells.