Characterization of forskolin-induced Ca2+ signals in rat olfactory receptor neurons.
Forskolin-induced Ca(2+) signals were examined in isolated rat olfactory receptor neurons (ORNs) using a Ca(2+) indicator, fura-2. In the soma of the ORNs, forskolin caused an increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) that was enhanced by a phosphodiesterase (PDE) 1 inhibitor, 8-methoxymethyl-3-isobutyl-1-methyl-xanthine, but not a PDE4 inhibitor, rolipram. Forskolin-induced Ca(2+) signals were abolished with the removal of extracellular Ca(2+) and un-affected by treatment with thapsigargin or caffeine plus ryanodine. Niflumic acid, a Ca(2+)-activated Cl(-) channel inhibitor, or nifedipine, an L-type Ca(2+) channel inhibitor, slowed the initial rate of the increase in [Ca(2+)](i) in response to forskolin. Nifedipine did not affect the increase in [Ca(2+)](i) that was slowed by niflumic acid. In Ca(2+) measurements with a confocal microscope and a calcium indicator, Fluo-4, the onset of the response to forskolin in the knob region occurred simultaneously or earlier, but not later, than that in the soma. It is suggested that the forskolin-induced Ca(2+) signals are due to Ca(2+) influx, but not the release of Ca(2+) from Ca(2+) stores, and that the initial rapid increase in [Ca(2+)](i) is associated with the activation of the voltage-dependent Ca(2+) channels in rat ORNs.
Otsuguro
Ken-ichi
K
Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. otsuguro@vetmed.hokudai.ac.jp
Gautam
Shree Hari
SH
Ito
Shigeo
S
Habara
Yoshiaki
Y
Saito
Toshiyuki
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D005576:Colforsin; D009544:Niflumic Acid; D016257:Fura-2