Glutamate regulates local and global Ca 2+ signals in myocytes of piglet brain slice arterioles through astrocyte‐ and heme oxygenase‐dependent mechanisms

Glutamate is the principal cerebral excitatory neurotransmitter and dilates cerebral arterioles to match blood flow to neural activity. Arterial contractility is regulated by local and global Ca 2+ signals that occur in myocytes, but modulation of these signals by glutamate is poorly understood. Using high‐speed confocal imaging we measured glutamate regulation of Ca 2+ signals that occur in myocytes within arterioles of piglet tangential brain slices. Glutamate elevated Ca 2+ spark frequency ~188% and reduced global intracellular Ca 2+ concentration ([Ca 2+ ] i ) to ~76% of control, but did not alter Ca 2+ waves. Cerebral arteriole isolation from brain slices abolished glutamate‐induced Ca 2+ signal modulation. In slices treated with L‐AAA, a glial toxin, glutamate did not alter Ca 2+ sparks or global [Ca 2+ ] i , but activated Ca 2+ waves. This shift in Ca 2+ signal modulation by glutamate did not occur in slices treated with D‐AAA, an inactive isomer of L‐AAA. In the presence of CrMP, a heme oxygenase blocker, glutamate inhibited Ca 2+ sparks and Ca 2+ waves and did not alter global [Ca 2+ ] i . Collectively, these data indicate that glutamate can modulate local and global Ca 2+ signals in arteriole myocytes via mechanisms that require astrocytes and heme‐oxygenase. In the absence of astrocytes or functional heme oxygenase, effects of glutamate on arterial Ca 2+ signals were absent or the opposite of those in the intact system.