Calcium Sparks Unleashed in Vascular Smooth Muscle

ypertension is a progressive disease involving an increase in arterial constriction.It constitutes a major risk factor leading to stroke, heart disease, and kidney failure.Understanding the molecular pathways involved in arterial tone regulation is crucial to increasing our understanding of blood pressure regulation.Recently, a novel mechanism involving small-localized bursts of calcium inside vascular smooth muscle cells, termed Ca 2ϩ sparks, was identified that acts as a negative feedback mechanism that opposes vasoconstriction. 1 Ca 2؉ Sparks in MuscleCa 2ϩ sparks are thought to be the elementary functional Ca 2ϩ release signals in heart, skeletal, and smooth muscle cells.1-4 Ca 2ϩ sparks are but one example of the increasing complexity in Ca 2ϩ signaling in the spatial and temporal domain in a variety of tissues including arterial smooth muscle.5 Ca 2ϩ sparks result from the opening of several or the coordinated opening of many, tightly clustered ryanodine receptor Ca 2ϩ release channels (RyRs) in the sarcoplasmic reticulum (SR) of muscle cells.6,7 In arterial smooth muscle and intact arteries, Ca 2ϩ sparks are observed just under the cell membrane consistent with a predominant subsarcolemmal localization of the RyR Ca 2ϩ release channels in the sarcoplasmic reticulum.3,8 Function, Distribution, and Localization of RyR Isoforms