Sarcoplasmic reticulum calcium load regulates rat arterial smooth muscle calcium sparks and transient K(Ca) currents.

Abstract

The regulation of calcium (Ca(2+)) sparks and transient calcium-sensitive K(+) (K(Ca)) currents by acute changes in sarcoplasmic reticulum (SR) Ca(2+) load ([Ca(2+)](SR)) was investigated in rat cerebral artery smooth muscle cells using laser-scanning confocal microscopy in combination with patch clamp electrophysiology. [Ca(2+)](SR) was elevated by: (i) increasing the activity of the SR Ca(2+)-ATPase with an anti-phospholamban monoclonal antibody, or (ii) blocking Ca(2+) release from the SR with tetracaine, a membrane-permeant, reversible ryanodine-sensitive Ca(2+) release (RyR) channel blocker. Alternatively, [Ca(2+)](SR) was progressively decreased over time with a low concentration of thapsigargin (20 nM), a SR Ca(2+)-ATPase blocker. An elevation in [Ca(2+)](SR) increased Ca(2+) spark and transient K(Ca) current frequency, but did not alter the amplitude, decay or spatial spread of Ca(2+) sparks or the coupling ratio or amplitude correlation between Ca(2+) sparks and evoked transient K(Ca) currents. Decreasing [Ca(2+)](SR) reduced Ca(2+) spark frequency, amplitude and spatial spread and this reduced transient K(Ca) current frequency and amplitude. However, even when mean Ca(2+) spark amplitude and spread decreased by up to 47 and 56 % of control, respectively, the coupling ratio or amplitude correlation between Ca(2+) sparks and transient K(Ca) currents was not affected. These data demonstrate that acute changes in [Ca(2+)](SR) regulate Ca(2+) sparks and transient K(Ca) currents in arterial smooth muscle cells.