Differential regulation of voltage-gated Ca 2+ currents and metabotropic glutamate receptor activity by measles virus infection in rat cortical neurons

摘要

Measles virus (MV) infection may lead to severe chronic CNS disease processes, including MV-induced encephalitis. Because the intracellular Ca 2+ concentration ([Ca 2+] i) is a major determinant of the (patho-)physiological state in all cells we asked whether important Ca 2+ conducting pathways are affected by MV infection in cultured cortical rat neurons. Patch-clamp measurements revealed a decrease in voltage-gated Ca 2+ currents during MV-infection, while voltage-gated K + currents and NMDA-evoked currents were unaffected. Calcium-imaging experiments using 50mM extracellular KCl showed reduced [Ca 2+] i increases in MV-infected neurons, confirming a decreased activity of voltage-gated Ca 2+ channels. In contrast, the group-I metabotropic glutamate receptor (mGluR) agonist DHPG evoked changes in [Ca 2+] i that were increased in MV-infected cells. Our results show that MV infection conversely regulates Ca 2+ signals induced by group-I mGluRs and by voltage-gated Ca 2+ channels, suggesting that these physiological impairments may contribute to an altered function of cortical neurons during MV-induced encephalitis.