T‐type calcium channels in carotid body oxygen sensing (889.1)
Vladislav V. Makarenko, Yingjie Peng, Lin Hua Piao, Jayasri Nanduri, Nanduri R. Prabhakar
Abstract
Vladislav V. Makarenko, Yingjie Peng, Lin Hua Piao, Jayasri Nanduri, Nanduri R. Prabhakar
Abstract
Previous studies showed that low voltage gated T‐type Ca 2+ channels play an important role in hypoxia‐evoked catecholamine secretion from adrenal chromaffin cells. The objective of the present study was to investigate whether T‐type Ca 2+ channels contribute to hypoxic sensing by the carotid body, a key sensory organ for detecting arterial blood O 2 levels. Real time quantitative PCR analysis of rat carotid body revealed relatively high levels of α 1H as compared to α 1G and α 1I subunits of T‐type Ca 2+ channels. Immunocytochemical analysis showed much of the α 1H protein in glomus cells. Mibefradil (1µM), a T‐type Ca 2+ channel blocker significantly attenuated the carotid body sensory and glomus cell secretory and [Ca 2+ ] i responses to hypoxia. Similar attenuation of glomus cell secretory as well as [Ca 2+ ] i responses were also seen in α 1H knockout mice. These results demonstrate that T‐type Ca 2+ channels contribute to carotid body and glomus cells response to hypoxia. Grant Funding Source : Supported by NIH‐HL‐90554
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Previous studies showed that low voltage gated T‐type Ca 2+ channels play an important role in hypoxia‐evoked catecholamine secretion from adrenal chromaffin cells. The objective of the present study was to investigate whether T‐type Ca 2+ channels contribute to hypoxic sensing by the carotid body, a key sensory organ for detecting arterial blood O 2 levels. Real time quantitative PCR analysis of rat carotid body revealed relatively high levels of α 1H as compared to α 1G and α 1I subunits of T‐type Ca 2+ channels. Immunocytochemical analysis showed much of the α 1H protein in glomus cells. Mibefradil (1µM), a T‐type Ca 2+ channel blocker significantly attenuated the carotid body sensory and glomus cell secretory and [Ca 2+ ] i responses to hypoxia. Similar attenuation of glomus cell secretory as well as [Ca 2+ ] i responses were also seen in α 1H knockout mice. These results demonstrate that T‐type Ca 2+ channels contribute to carotid body and glomus cells response to hypoxia. Grant Funding Source : Supported by NIH‐HL‐90554
Key concepts: Glomus cell, Carotid body, Mibefradil, Hypoxia (environmental), Endocrinology, Internal medicine, Voltage-dependent calcium channel, Chemistry