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NFATc3 regulates Kv2.1 expression in arterial smooth muscle
Gregory C Amberg1, Charles F Rossow, Manuel F Navedo
1Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA.
The Journal of Biological Chemistry
|August 24, 2004
Summary
Angiotensin II reduces arterial smooth muscle excitability by decreasing Kv2.1 expression via calcineurin and NFATc3. This pathway regulates voltage-gated potassium (Kv) channel function in blood vessels.
Area of Science:
- Cardiovascular physiology
- Molecular biology
- Smooth muscle function
Background:
- Voltage-gated potassium (Kv) channels are crucial for regulating arterial smooth muscle excitability.
- The precise molecular mechanisms governing Kv channel regulation in smooth muscle are not fully understood.
Purpose of the Study:
- To investigate if angiotensin II (Ang II) modulates arterial smooth muscle Kv channel function through calcineurin-dependent NFAT activation.
- To elucidate the role of NFATc3 in regulating Kv channel expression and function in response to Ang II.
Main Methods:
- Examined the effect of sustained Ang II administration on Kv currents (IKv) and Kv2.1 subunit expression in arterial smooth muscle.
- Investigated the involvement of calcium (Ca2+) influx, calcineurin, and NFATc3 in the Ang II-mediated signaling pathway.
Main Results:
- Sustained Ang II administration decreased IKv by reducing Kv2.1 expression, independent of pressure but dependent on L-type Ca2+ channel activity.
- Calcineurin and NFATc3 were identified as essential components in the signaling cascade that reduces IKv in response to Ang II.
Conclusions:
- Sustained Ang II exposure activates calcineurin and NFATc3 via increased smooth muscle Ca2+, leading to reduced Kv2.1 expression and impaired IKv function.
- NFATc3 plays a novel role in controlling arterial smooth muscle excitability by regulating Kv2.1 expression.