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Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity

Department of Aerospace Physiology, The Fourth Military Medical University, Xi'an 710032, China

Submitted 17 February 2004 ; accepted in final form 4 May 2004

The purpose of this study was to test the hypothesis that differential autoregulation of cerebral and hindquarter arteries during simulated microgravity is mediated or modulated by differential activation of K⁺ channels in vascular smooth muscle cells (VSMCs) of arteries in different anatomic regions. Sprague-Dawley rats were subjected to 1- and 4-wk tail suspension to simulate the cardiovascular deconditioning effect due to short- and medium-term microgravity. K⁺ channel function of VSMCs was studied by pharmacological methods and patch-clamp techniques. Large-conductance Ca²⁺-activated K⁺ (BK_Ca) and voltage-gated K⁺ (K_v) currents were determined by subtracting the current recorded after applications of 1 mM tetraethylammonium (TEA) and 1 mM TEA + 3 mM 4-aminopyridine (4-AP), respectively, from that of before. For cerebral vessels, the normalized contractility of basilar arterial rings to TEA, a BK_Ca blocker, and 4-AP, a K_v blocker, was significantly decreased after 1- and 4-wk simulated microgravity, respectively. VSMCs isolated from the middle cerebral artery branches of suspended rats had a more depolarized membrane potential (E_m) and a smaller K⁺ current density compared with those of control rats. Furthermore, the reduced total current density was due to smaller BK_Ca and smaller K_v current density in cerebral VSMCs after 1- and 4-wk tail suspension, respectively. For hindquarter vessels, VSMCs isolated from second- to sixth-order small mesenteric arteries of both 1- and 4-wk suspended rats had a more negative E_m and larger K⁺ current densities for total, BK_Ca, and K_v currents. These results indicate that differential activation of K⁺ channels occur in cerebral and hindquarter VSMCs during short- and medium-term simulated microgravity. It is further suggested that different profiles of channel remodeling might occur in VSMCs as one of the important underlying cellular mechanisms to mediate and modulate differential vascular adaptation during microgravity.

hindlimb unloading; ion channels; vessels; voltage-dependent potassium channels; calcium-dependent potassium channels

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