The Role of IP3 Receptors in Generating Calcium Waves and Cerebral Myogenic Tone

Abstract

This study of the cerebral vasculature examined whether: 1) elevated intravascular pressure induces asynchronous Ca2+ waves by activating IP3 receptors; and 2) these events drive myogenic tone development by augmenting myosin light chain phosphorylation (LC20). Rat cerebral arteries pressurized between 20–100 mmHg were examined in the absence and presence of agents that deplete the sarcoplasmic reticulum (SR) of Ca2+ or block IP3 receptors. Diameter and membrane potential (VM) were assessed using conventional techniques whereas Ca2+ waves and LC20 phosphorylation were monitored using confocal microscopy and western blot analysis, respectively. Elevated intravascular pressure increased the proportion of smooth muscle cells firing Ca2+ waves as well as the frequency of these voltage‐independent events. Agents that deplete the SR of Ca2+ (ryanodine, CPA and Thapsigargin) or block IP3 receptors (2‐APB or Xestospongin‐C) eliminated Ca2+ wave generation. The loss of Ca2+ waves attenuated LC20 phosphorylation and attenuated myogenic tone development. It did not, however, alter pressure‐induced depolarization in an intact artery In summary, this study shows that pressure‐induced Ca2+ waves facilitate cerebral myogenic tone by providing a proportion of the Ca2+ required to activate myosin light chain kinase. Supported by NSERC.