Emergence of a R-Type Ca 2+ Channel (Ca V 2.3) Contributes to Cerebral Artery Constriction After Subarachnoid Hemorrhage
| Autor: | Masanori Ishiguro, Theresa L. Wellman, Akira Honda, Sheila R. Russell, Bruce I. Tranmer, George C. Wellman |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Dihydropyridines medicine.medical_specialty Patch-Clamp Techniques Subarachnoid hemorrhage Calcium Channels L-Type Nifedipine Physiology Myocytes Smooth Muscle Cerebral arteries Drug Resistance Spider Venoms Calcium Channels R-Type Cisterna magna Muscle Smooth Vascular Injections Constriction Diltiazem Cerebral vasospasm omega-Agatoxin IVA omega-Conotoxin GVIA Internal medicine Cisterna Magna medicine Animals Vasospasm Intracranial cardiovascular diseases Ion Transport Voltage-dependent calcium channel business.industry Calcium channel Vasospasm Cerebral Arteries Subarachnoid Hemorrhage Calcium Channel Blockers medicine.disease Disease Models Animal Blood Vasoconstriction Anesthesia Cardiology Calcium Rabbits Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation Research. 96:419-426 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.0000157670.49936.da |
| Popis: | Cerebral aneurysm rupture and subarachnoid hemorrhage (SAH) inflict disability and death on thousands of individuals each year. In addition to vasospasm in large diameter arteries, enhanced constriction of resistance arteries within the cerebral vasculature may contribute to decreased cerebral blood flow and the development of delayed neurological deficits after SAH. In this study, we provide novel evidence that SAH leads to enhanced Ca 2+ entry in myocytes of small diameter cerebral arteries through the emergence of R-type voltage-dependent Ca 2+ channels (VDCCs) encoded by the gene Ca V 2.3. Using in vitro diameter measurements and patch clamp electrophysiology, we have found that L-type VDCC antagonists abolish cerebral artery constriction and block VDCC currents in cerebral artery myocytes from healthy animals. However, 5 days after the intracisternal injection of blood into rabbits to mimic SAH, cerebral artery constriction and VDCC currents were enhanced and partially resistant to L-type VDCC blockers. Further, SNX-482, a blocker of R-type Ca 2+ channels, reduced constriction and membrane currents in cerebral arteries from SAH animals, but was without effect on cerebral arteries of healthy animals. Consistent with our biophysical and functional data, cerebral arteries from healthy animals were found to express only L-type VDCCs (Ca V 1.2), whereas after SAH, cerebral arteries were found to express both Ca V 1.2 and Ca V 2.3. We propose that R-type VDCCs may contribute to enhanced cerebral artery constriction after SAH and may represent a novel therapeutic target in the treatment of neurological deficits after SAH. |
| Databáze: | OpenAIRE |
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