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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/H1304    most recent 00528.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pluteanu, F. Articles by Cribbs, L. L. PubMed PubMed Citation Articles by Pluteanu, F. Articles by Cribbs, L. L.

T-type calcium channels are regulated by hypoxia/reoxygenation in ventricular myocytes

Departments of Medicine and Physiology, Cardiovascular Institute, Loyola University Chicago, Maywood, Illinois

Submitted June 11, 2009 ; accepted in final form August 3, 2009

Low-voltage-activated calcium channels are reexpressed in ventricular myocytes in pathological conditions associated with hypoxic episodes, but a direct relation between oxidative stress and T-type channel function and regulation in cardiomyocytes has not been established. We aimed to investigate low-voltage-activated channel regulation under oxidative stress in neonatal rat ventricular myocytes. RT-PCR measurements of voltage-gated Ca²⁺ (Ca_v)3.1 and Ca_v3.2 mRNA levels in oxidative stress were compared with whole cell patch-clamp recordings of T-type calcium current. The results indicate that hypoxia reduces T-type current density at –30 mV (the hallmark of this channel) based on the shift of the voltage dependence of activation to more depolarized values and downregulation of Ca_v3.1 at the mRNA level. Upon reoxygenation, both Ca_v3.1 mRNA levels and the voltage dependence of total T-type current are restored, although differently for activation and inactivation. Using Ni²⁺, we distinguished different effects of hypoxia/reoxygenation on the two current components. Long-term incubation in the presence of 100 µM CoCl₂ reproduced the effects of hypoxia on T-type current activation and inactivation, indicating that the chemically induced oxidative state is sufficient to alter T-type calcium current activity, and that hypoxia-inducible factor-1 is involved in Ca_v3.1 downregulation. Our results demonstrate that Ca_v3.1 and Ca_v3.2 T-type calcium channels are differentially regulated by hypoxia/reoxygenation injury, and, therefore, they may serve different functions in the myocyte in response to hypoxic injury.

low-voltage-activated calcium channel; oxidative stress; cardiomyocytes