title: Glutamate regulates Ca2+ signals in smooth muscle cells of newborn piglet brain slice arterioles through astrocyte- and heme oxygenase-dependent mechanisms.
abstract: 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 smooth muscle cells, but modulation of these signals by glutamate is poorly understood. Here, using high-speed confocal imaging, we measured the Ca(2+) signals that occur in arteriole smooth muscle cells of newborn piglet tangential brain slices, studied signal regulation by glutamate, and investigated the physiological function of heme oxygenase (HO) and carbon monoxide (CO) in these responses. Glutamate elevated Ca(2+) spark frequency by approximately 188% and reduced global intracellular Ca(2+) concentration ([Ca(2+)](i)) to approximately 76% of control but did not alter Ca(2+) wave frequency in brain arteriole smooth muscle cells. Isolation of cerebral arterioles from brain slices abolished glutamate-induced Ca(2+) signal modulation. In slices treated with l-2-alpha-aminoadipic acid, a glial toxin, glutamate did not alter Ca(2+) sparks or global [Ca(2+)](i) but did activate Ca(2+) waves. This shift in Ca(2+) signal modulation by glutamate did not occur in slices treated with d-2-alpha-aminoadipic acid, an inactive isomer of l-2-alpha-aminoadipic acid. In the presence of chromium mesoporphyrin, a HO blocker, glutamate inhibited Ca(2+) sparks and Ca(2+) waves and did not alter global [Ca(2+)](i). In isolated arterioles, CORM-3 [tricarbonylchloro(glycinato)ruthenium(II)], a CO donor, activated Ca(2+) sparks and reduced global [Ca(2+)](i). These effects were blocked by 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one, a soluble guanylyl cyclase inhibitor. Collectively, these data indicate that glutamate can modulate Ca(2+) sparks, Ca(2+) waves, and global [Ca(2+)](i) in arteriole smooth muscle cells via mechanisms that require astrocytes and HO. These data also indicate that soluble guanylyl cyclase is involved in CO activation of Ca(2+) sparks in arteriole smooth muscle cells.
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors: Qi
authors: Q
authors: Xi
authors: Edward
authors: E
authors: Umstot
authors: Guiling
authors: G
authors: Zhao
authors: Damodaran
authors: D
authors: Narayanan
authors: Charles W
authors: CW
authors: Leffler
authors: Jonathan H
authors: JH
authors: Jaggar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002248:Carbon Monoxide / Q000378:metabolism; D002450:Cell Communication; D018698:Glutamic Acid / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008652:Mesoporphyrins / Q000494:pharmacology; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology; D013552:Swine
chemical_list: D008652:Mesoporphyrins; D009942:Organometallic Compounds; C427471:chromium mesoporphyrin; C476530:tricarbonylchloro(glycinato)ruthenium(II); D018698:Glutamic Acid; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D002118:Calcium