Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone. J Cereb Blood Flow Metab 2011 Jan;31(1):3-16
Date
08/26/2010Pubmed ID
20736958Pubmed Central ID
PMC3049462DOI
10.1038/jcbfm.2010.143Scopus ID
2-s2.0-78650876681 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
Intracellular Ca(2+) release events ('Ca(2+) sparks') and transient activation of large-conductance Ca(2+)-activated potassium (BK) channels represent an important vasodilator pathway in the cerebral vasculature. Considering the frequent occurrence of cerebral artery constriction after subarachnoid hemorrhage (SAH), our objective was to determine whether Ca(2+) spark and BK channel activity were reduced in cerebral artery myocytes from SAH model rabbits. Using laser scanning confocal microscopy, we observed ∼50% reduction in Ca(2+) spark activity, reflecting a decrease in the number of functional Ca(2+) spark discharge sites. Patch-clamp electrophysiology showed a similar reduction in Ca(2+) spark-induced transient BK currents, without change in BK channel density or single-channel properties. Consistent with a reduction in active Ca(2+) spark sites, quantitative real-time PCR and western blotting revealed decreased expression of ryanodine receptor type 2 (RyR-2) and increased expression of the RyR-2-stabilizing protein, FKBP12.6, in the cerebral arteries from SAH animals. Furthermore, inhibitors of Ca(2+) sparks (ryanodine) or BK channels (paxilline) constricted arteries from control, but not from SAH animals. This study shows that SAH-induced decreased subcellular Ca(2+) signaling events disable BK channel activity, leading to cerebral artery constriction. This phenomenon may contribute to decreased cerebral blood flow and poor outcome after aneurysmal SAH.
Author List
Koide M, Nystoriak MA, Krishnamoorthy G, O'Connor KP, Bonev AD, Nelson MT, Wellman GCAuthor
Gayathri K. Natarajan Research Scientist I in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Calcium Signaling
Cerebral Arteries
Cerebrovascular Circulation
Cytosol
Electrophysiological Phenomena
Homeostasis
Male
Muscle Tonus
Muscle, Smooth, Vascular
Nervous System Diseases
Patch-Clamp Techniques
Potassium Channels, Calcium-Activated
Pressure
RNA
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Ryanodine Receptor Calcium Release Channel
Subarachnoid Hemorrhage
Tacrolimus Binding Proteins
Vasoconstriction
