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Angiotensin II Inhibits T‐type Ca 2+ Channels in Cerebral Arterial Smooth Muscle Cells
Author(s) -
Hashad Ahmed Mohamed,
Sancho Maria,
Welsh Donald
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.945.12
Subject(s) - angiotensin ii , nadph oxidase , losartan , chemistry , patch clamp , protein kinase c , vascular smooth muscle , endocrinology , medicine , myocyte , cerebral arteries , gq alpha subunit , reactive oxygen species , biophysics , receptor , signal transduction , biology , biochemistry , g protein , smooth muscle
T‐type Ca 2+ channels (Ca V 3.1 and Ca V 3.2) are expressed in cerebral arterial smooth muscle cells and they play a key role in regulating arterial tone. In this study, we investigated whether and by what mechanism Angiotensin II (Ang II), a vasoactive peptide produced within the cerebral arterial wall, influences T‐type Ca 2+ channels. Using patch clamp electrophysiology and rat cerebral arterial myocytes, Ang II (100 nM) was shown to inhibit T‐type Ca 2+ currents in a time‐dependent manner (~ 40% after 15 min); it also shifted the voltage‐dependency of activation by 7 mV. Ang II induced inhibition was mediated through the AT 1 receptor, as preincubation with Losartan (1 μM) abolished the effect. Protein kinase C (PKC) blockade by GF 109203X (100 nM) did not eliminate Ang II‐mediated inhibition, demonstrating that this signaling protein was not involved. In contrast, NADPH oxidase inhibitors abolished the inhibitory effect of Ang II revealing a role for reactive oxygen species (ROS) on T‐type Ca 2+ channels. To delineate if Ang II is targeting a particular T‐type channel, Ni 2+ (50 μM) was added to selectively block Ca V 3.2. In the presence of Ni 2+ , Ang II did not induce further inhibition of the residual current, indicating that Ang II was selectively targeting Ca V 3.2. In summary, Ang II inhibits Ca V 3.2 channels in cerebral myocytes through the generation of ROS. These findings suggest that T‐type channels are a regulatory target of vasoactive stimuli, known to facilitate the “constrictive” phenotype prevalent with cerebrovascular disease. Support or Funding Information Canadian Institutes of Health Research, Alberta Innovates Health Solutions, Vanier Graduate Scholarship (CIHR)