The Role of Voltage-Dependent Calcium Channels and IP3 Receptors in Lymphatic Contractility

Abstract

Through the lymphatic system’s unique ability to phasically contract, it plays critical roles in maintaining tissue fluid and macromolecular homeostasis, lipid absorption, and immune function. These contractions are promoted by stretch-activation, trigger by increases in intraluminal pressure, leading to an increase in the rate of phasic contractions. Moreover, these phasic contractions are driven by changes in electrical activity and an increase in intracellular calcium levels dependent upon extracellular calcium entry through voltage-dependent calcium channels (VDCCs) and calcium release from the sarcoplasmic reticulum (SR) stores through inositol triphosphate (IP3) receptors. While the involvement of these players in smooth muscle contractions have been well documented, they have not been characterized in lymphatic vessels. Using pressure- and wire-myography, electrophysiology, Polymerase Chain Reaction (PCR) and immunofluorescence imaging, we investigated the role of VDCCs and IP3 receptors on contractile and electrophysiological properties of stretch-activated contractions in isolated rat mesenteric lymphatic vessels.