title: Spatiotemporal dynamics of intracellular calcium in the middle cerebral artery isolated from stroke-prone spontaneously hypertensive rats.
abstract: The spatiotemporal dynamics of intracellular calcium within the middle cerebral artery (MCA) isolated from stroke-prone spontaneously hypertensive rats (SHR-SP) were investigated using real-time confocal laser microscopy. At 3 months of age (prestroke), rhythmical changes in the [Ca(2+)](i) during the tonic phase were found to precede vasomotion following application of 5-HT, but not other stimuli. These responses were not observed at 1 month of age; moreover, the MCA lost both responses post-stroke (5 months of age). When [Ca(2+)](i) was analysed in arteriolar smooth muscle cells, rhythmical changes in [Ca(2+)](i) occurred during the same cycle. Thus, these processes were synchronized. The synchronized rhythmical changes in [Ca(2+)](i) were abolished following application of 100 nM ketanserin and 10 μM nicardipine. Treatment with 60 nM charybdotoxin and 10 μM cyclopiazonic acid also significantly reduced rhythmical elevations in [Ca(2+)](i). In addition, rhythmical changes in [Ca(2+)](i) became unsynchronized following treatment with 100 μM carbenoxolone, a gap junction blocker. Connexin 45 mRNA and protein expression were both elevated in the MCA of SHR-SP. Taken together, these findings suggest that rhythmical changes in [Ca(2+)](i) of the MCA are dependent upon the 5-HT(2) receptor-mediated release of calcium from intracellular stores which, in turn, activates voltage-dependent calcium channels to enable an influx of calcium into smooth muscle cells. Subsequently, charybdotoxin-sensitive potassium channels are activated and provide a negative feedback pathway to regulate [Ca(2+)](i). Moreover, the co-ordinated synchronization of rhythmical changes in [Ca(2+)](i) across smooth muscle cells was found to be dependent upon gap junctions.
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. t-hashi@pharm.showa-u.ac.jp
authors: Terumasa
authors: T
authors: Hashimoto
authors: Mariko
authors: M
authors: Kiya
authors: Hisayuki
authors: H
authors: Ohata
authors: Takuro
authors: T
authors: Miyazaki
authors: Keita
authors: K
authors: Shibata
authors: Koji
authors: K
authors: Nobe
authors: Kazuo
authors: K
authors: Honda
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism; D008297:Male; D020768:Middle Cerebral Artery / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D020521:Stroke / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D017630:Connexins; D024681:Potassium Channels, Calcium-Activated; D044348:Receptors, Serotonin, 5-HT2; C082920:connexin 45; D012701:Serotonin; D002118:Calcium