Differential regulation of voltage-gated Ca2+ currents and metabotropic glutamate receptor activity by measles virus infection in rat cortical neurons.
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.
Institute of Virology, University Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
Christine
C
Günther
Mandy
M
Laube
Uwe-Gerd
UG
Liebert
Robert
R
Kraft
D000818:Animals; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008459:Measles virus / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D014764:Viral Proteins; D008734:Methoxyhydroxyphenylglycol; D016202:N-Methylaspartate; D011189:Potassium Chloride; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol