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.
journal_name
Exp Physioljournal_title
Experimental physiologyauthors
Hashimoto T,Kiya M,Ohata H,Miyazaki T,Shibata K,Nobe K,Honda Kdoi
10.1113/expphysiol.2011.061499subject
Has Abstractpub_date
2012-02-01 00:00:00pages
265-76issue
2eissn
0958-0670issn
1469-445Xpii
expphysiol.2011.061499journal_volume
97pub_type
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