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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1371    most recent 01368.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Figueroa, X. F. Articles by Duling, B. R. Search for Related Content PubMed PubMed Citation Articles by Figueroa, X. F. Articles by Duling, B. R.

Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?

¹Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; ²Institute of Biomedical Science, Academia Sinica, Nankang, Taipei, Taiwan; ³Howard Hughes Medical Institute and Departments of ⁴Physiology and Biophysics and ⁵Neurology, University of Iowa, Iowa City, Iowa; and ⁶Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia

Submitted 14 December 2006 ; accepted in final form 18 May 2007

In the microcirculation, longitudinal conduction of vasomotor responses provides an essential means of coordinating flow distribution among vessels in a complex network. Spread of current along the vessel axis can display a regenerative component, which leads to propagation of vasomotor signals over many millimeters; the ionic basis for the regenerative response is unknown. We examined the responses to 10 s of focal electrical stimulation (30 Hz, 2 ms, 30 V) of mouse cremaster arterioles to test the hypothesis that voltage-dependent Na⁺ (Na_v) and Ca²⁺ channels might be activated in long-distance signaling in microvessels. Electrical stimulation evoked a vasoconstriction at the site of stimulation and a spreading, nondecremental conducted dilation. Endothelial damage (air bubble) blocked conduction of the vasodilation, indicating an involvement of the endothelium. The Na_v channel blocker bupivacaine also blocked conduction, and TTX attenuated it. The Na_v channel activator veratridine induced an endothelium-dependent dilation. The Na_v channel isoforms Na_v1.2, Na_v1.6, and Na_v1.9 were detected in the endothelial cells of cremaster arterioles by immunocytochemistry. These findings are consistent with the involvement of Na_v channels in the conducted response. BAPTA buffering of endothelial cell Ca²⁺ delayed and reduced the conducted dilation, which was almost eliminated by Ni²⁺, amiloride, or deletion of _1H T-type Ca²⁺ (Ca_v3.2) channels. Blockade of endothelial nitric oxide synthase or Ca²⁺-activated K⁺ channels also inhibited the conducted vasodilation. Our findings indicate that an electrically induced signal can propagate along the vessel axis via the endothelium and can induce sequential activation of Na_v and Ca_v3.2 channels. The resultant Ca²⁺ influx activates endothelial nitric oxide synthase and Ca²⁺-activated K⁺ channels, triggering vasodilation.

conducted vasodilation; T-type calcium channels; hypertension; gap junction; voltage-gated sodium channels