Activation of Endothelial Transient Receptor Potential C3 Channel Is Required for Small Conductance Calcium‐Activated Potassium Channel Activation and Sustained Endothelial Hyperpolarization and Vasodilation of Cerebral Artery

Autor: Mikhail Y. Kochukov, Adithya Balasubramanian, Lutz Birnbaumer, Sean P. Marrelli, Joel Abramowitz
Rok vydání: 2014
Předmět:
Patch-Clamp Techniques
vasculature
Small-Conductance Calcium-Activated Potassium Channels
Vasodilation
Vascular Medicine
Membrane Potentials
purl.org/becyt/ford/1 [https]
Mice
Transient receptor potential channel
0302 clinical medicine
TRPC3
VASCULATURE
endothelium‐derived factors
Original Research
Mice
Knockout
Membrane potential
0303 health sciences
ion channels
Bioquímica y Biología Molecular
Hyperpolarization (biology)
medicine.anatomical_structure
ENDOTHELIUM-DERIVED FACTORS
cerebrovascular circulation
Cardiology and Cardiovascular Medicine
CIENCIAS NATURALES Y EXACTAS
medicine.medical_specialty
endothelium
Endothelium
Ciencias Biológicas
03 medical and health sciences
Internal medicine
ION CHANNELS
medicine
Animals
purl.org/becyt/ford/1.6 [https]
Ion channel
TRPC Cation Channels
030304 developmental biology
Posterior Cerebral Artery
business.industry
Endothelial Cells
Calcium-activated potassium channel
Endocrinology
ENDOTHELIUM
Biophysics
Calcium
Endothelium
Vascular
CEREBROVASCULAR CIRCULATION
business
030217 neurology & neurosurgery
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
DOI: 10.1161/jaha.114.000913
Popis: Background Transient receptor potential C3 ( TRPC 3) has been demonstrated to be involved in the regulation of vascular tone through endothelial cell ( EC ) hyperpolarization and endothelium‐dependent hyperpolarization–mediated vasodilation. However, the mechanism by which TRPC 3 regulates these processes remains unresolved. We tested the hypothesis that endothelial receptor stimulation triggers rapid TRPC 3 trafficking to the plasma membrane, where it provides the source of Ca 2+ influx for small conductance calcium‐activated K + (SK Ca ) channel activation and sustained EC hyperpolarization. Methods and Results Pressurized artery studies were performed with isolated mouse posterior cerebral artery. Treatment with a selective TRPC 3 blocker (Pyr3) produced significant attenuation of endothelium‐dependent hyperpolarization–mediated vasodilation and endothelial Ca 2+ response ( EC ‐specific Ca 2+ biosensor) to intraluminal ATP . Pyr3 treatment also resulted in a reduced ATP ‐stimulated global Ca 2+ and Ca 2+ influx in primary cultures of cerebral endothelial cells. Patch‐clamp studies with freshly isolated cerebral EC s demonstrated 2 components of EC hyperpolarization and K + current activation in response to ATP . The early phase was dependent on intermediate conductance calcium‐activated K + channel activation, whereas the later sustained phase relied on SK C a channel activation. The SK C a channel–dependent phase was completely blocked with TRPC 3 channel inhibition or in ECs of TRPC 3 knockout mice and correlated with increased trafficking of TRPC 3 (but not SK C a channel) to the plasma membrane. Conclusions We propose that TRPC 3 dynamically regulates SK C a channel activation through receptor‐dependent trafficking to the plasma membrane, where it provides the source of Ca 2+ influx for sustained SK C a channel activation, EC hyperpolarization, and endothelium‐dependent hyperpolarization–mediated vasodilation.
Databáze: OpenAIRE
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