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Human Ca V 1.2/Ca V 3.x channels mediate paradoxical vasomotor responses in the human cerebral circulation (677.11)
Author(s) -
Harraz Osama,
Visser Frank,
Brett Suzanne,
Zechariah Anil,
Watson Tim,
Me Bijoy,
Starreveld Yves,
Welsh Donald
Publication year - 2014
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.28.1_supplement.677.11
Subject(s) - cerebral circulation , electrical impedance myography , patch clamp , cerebral arteries , electrophysiology , gene isoform , vasomotor , chemistry , cerebral blood flow , vascular smooth muscle , western blot , biophysics , anatomy , medicine , neuroscience , endocrinology , vasodilation , biology , smooth muscle , biochemistry , gene
This study examined which voltage‐gated Ca 2+ channels are expressed in the human cerebral circulation and investigated their electrical and functional properties. Using cerebral arteries collected from patients undergoing resection surgeries, quantitative PCR and Western blot analyses revealed the expression of both L‐ and T‐type channels in the smooth muscle cell layer. Analogous to rodent, we observed both Ca V 1.2 (L) and Ca V 3.2 (T); intriguingly, Ca V 3.1 isoform was replaced in humans with Ca V 3.3 (T). Patch‐clamp electrophysiology displayed a robust whole‐cell Ba 2+ current whose amplitude varied inversely with the patients’ age. This inward current was subdivided into L‐ and T‐type components using standard pharmacological/electrical approaches. The T‐type conductance was further separated into Ca V 3.2 and Ca V 3.3 components by exploiting their differential sensitivity to Ni 2+ . Vessel myography revealed a key role for Ca V 1.2 and Ca V 3.3 channels in mediating cerebral arterial constriction with the former and latter predominating at depolarized and hyperpolarized voltages, respectively. Like the rodent, human Ca V 3.2 appears to drive a negative feedback response that antagonizes myogenic tone development. In conclusion, this study is the first to document three distinct Ca 2+ channel isoforms in human cerebral arteries along with their unique contribution to arterial tone development.