Analyses of Ca-related ion channel currents and their involvement in Ca mobilization in smooth muscle and endothelial cells

Abstract

Changes in intracellular Ca concentration ([Ca2+]i) play dominant roles in the regulation of ion channel activity. Thus, analyses of Ca-related ion channels, whose activation is responsible for and/or dependent on the changes in [Ca2+]i, are important to understand the physiological and pharmacological characteristics of smooth muscle cells (SMCs) and endothelial cells (ECs). We have clarified that, in SMCs, Ca mobilization by membrane depolarization and bioactive substances affects the activity of Ca-activated K (IK-Ca) and Cl channel currents. On the other hand, by measuring IK-Ca as an indicator of Ca mobilization, we found that palmitoylcarnitine (PC), a lipid released under ischemic conditions, mobilizes Ca in ECs via stimulation of endothelial differential gene (Edg) receptors. Moreover, sphingosine-1-phosphate, which is a lipid mediator and has a similar structure to PC, elevated [Ca2+]i in ECs via the activation of cation channels through Edg1 receptors. A myo-endothelial interaction is another regulatory factor of Ca mobilization in ECs as well as in SMCs. Nifedipine and levcromakalim, which have no effects on ion channels in ECs themselves, changed the membrane potential of ECs via a myo-endothelial pathway. These integral analyses provide better understanding of the functional roles of Ca-related ion channels and their involvement in Ca mobilization in SMCs and ECs.