The Role of L- and T-Type Calcium Channels in Local and Remote Calcium Responses in Rat Mesenteric Terminal Arterioles

Abstract

Background/Aims: The roles of intercellular communication and T-type versus L-type voltage-dependent Ca²⁺ channels (VDCCs) in conducted vasoconstriction to local KCl-induced depolarization were investigated in mesenteric arterioles. Methods: Ratiometric Ca²⁺ imaging (R) using Fura-PE3 with micro-ejection of depolarizing KCl solution and VDCC blockers, and immunohistochemical and RT-PCR techniques were applied to isolated rat mesenteric terminal arterioles (n = 71 from 47 rats; intraluminal diameter: 24 ± 1 μm; length: 550–700 μm). Results: Local application of KCl (at 0 μm) led to local (ΔR = 0.54) and remote (ΔR = 0.17 at 500 μm) increases in intracellular Ca²⁺. Remote Ca²⁺ responses were inhibited by the gap junction uncouplers carbenoxolone and palmitoleic acid. Ca_V1.2, Ca_V3.1 and Ca_V3.2 channels were immunolocalized in vascular smooth muscle cells and Ca_V3.2 in adjacent endothelial cells. Local and remote Ca²⁺ responses were inhibited by bath application of L- and T-type blockers [nifedipine, NNC 55-0396 and R(–)-efonidipine]. Remote Ca²⁺ responses (500 μm) were not affected by abolishing Ca²⁺ entry at an intermediate position on the arterioles (at 200–300 μm) using micro-application of VDCC blockers. Conclusion: Both L- and T-type channels mediate Ca²⁺ entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se.