G-proteins are involved in riluzole inhibition of high voltage-activated calcium channels in rat dorsal root ganglion neurons.
Effects of riluzole on high voltage-activated (HVA) calcium channels of rat dorsal root ganglion neurons were studied using the whole-cell patch-clamp technique. Riluzole at 30 microM inhibited the HVA currents. The onset and offset of riluzole inhibitory effect were slow usually taking more than 3 min. Riluzole inhibition of the HVA currents was abolished and partially reduced by addition of 500 microM GDP-beta-S and 1 mM N-ethylmaleimide, respectively, to the pipette solution. Pre-treatment with pertussis toxin or application of depolarizing pre-pulses did not affect riluzole's inhibitory effect on the HVA currents. Riluzole inhibition of the HVA currents was also blocked by internal application of 50 microg/ml protein kinase A inhibitory peptide. It was concluded that pertussis toxin-insensitive G-proteins and protein kinase A may be involved in riluzole inhibition of the HVA currents.
Huang
C S
CS
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Song
J H
JH
Nagata
K
K
Twombly
D
D
Yeh
J Z
JZ
Narahashi
T
T
D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D013844:Thiazoles; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D019782:Riluzole; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide