Role of voltage‐dependent calcium channels in stretch‐induced lymphatic vessel contractions

Abstract

Lymph drainage maintains tissue fluid homeostasis and facilitates immune response. It is promoted by phasic contractions of lymphatic vessels, which increase in rate with increase in luminal pressure. The contractions depend on activation of voltage‐dependent calcium channel (VDCC), which have not been characterized in lymphatic vessels. We used pressure‐ and wire‐myography, electrophysiology, PCR and immunofluorescence imaging to investigate the electrophysiological properties of L‐type and T‐type VDCCs and their role on stretch‐induced lymphatic contractions.Members of the VDCC family were expressed at the messenger RNA and protein level in rat mesenteric lymphatic vessels. The stretch‐induced increase in force was significantly attenuated in the presence of L‐type VDCC blockers nifedipine and diltiazem, while the T‐type VDCC blockers mibefradil and nickel significantly decreased the stretch‐induced increase in contraction frequency. Furthermore, nifedipine and diltiazem depolarized, while mibefradil and nickel hyperpolarized lymphatic muscle membrane potential.Our data suggest a delineating role of VDCCs in stretch‐induced lymphatic vessel contractions. We propose that activation of T‐type VDCC depolarizes membrane potential, regulating the frequency of lymphatic contractions via opening of L‐type VDCCs, which drive the strength of contractions.Supported by NIH