title: Acute and chronic effects of oxyhemoglobin on voltage-dependent ion channels in cerebral arteries.
abstract: Voltage-dependent potassium (Kv) and calcium (VDCC) channels play an important role in the regulation of membrane potential and intracellular calcium concentration in cerebral artery myocytes. Recent evidence suggests VDCC activity is increased and Kv channel activity is decreased in cerebral arteries following subarachnoid hemorrhage (SAH), promoting enhanced constriction. We have examined the impact of the blood component oxyhemoglobin on Kv and VDCC function in small (100-200 microm) diameter cerebral arteries. Acute (10 min) exposure of oxyhemoglobin caused cerebral artery constriction and Kv current suppression that was abolished by tyrosine kinase inhibitors and a Kv channel blocker. Although short-term oxyhemoglobin application did not directly alter VDCC activity, five-day exposure to oxyhemoglobin was associated with enhanced expression of voltage-dependent calcium channels. This work suggests that acute and chronic effects of oxyhemoglobin act synergistically to promote membrane depolarization and increased VDCC activity in cerebral arteries. These actions of oxyhemoglobin may contribute to the development of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
authors.affiliation: Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vermont 05405-0068, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ishiguro
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Link
authors.forename: K
authors.initials: K
authors.lastname: Zvarova
authors.forename: B I
authors.initials: BI
authors.lastname: Tranmer
authors.forename: A D
authors.initials: AD
authors.lastname: Morielli
authors.forename: G C
authors.initials: GC
authors.lastname: Wellman
mesh_terms: D000818:Animals; D020908:Calcium Channels, R-Type / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D009924:Organ Culture Techniques; D010108:Oxyhemoglobins / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D020908:Calcium Channels, R-Type; D007473:Ion Channels; D010108:Oxyhemoglobins