Characterization of Forskolin-Induced Ca²⁺ Signals in Rat Olfactory Receptor Neurons

Abstract

Forskolin-induced Ca²⁺ signals were examined in isolated rat olfactory receptor neurons (ORNs) using a Ca²⁺ indicator, fura-2. In the soma of the ORNs, forskolin caused an increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_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 Ca²⁺ signals were abolished with the removal of extracellular Ca²⁺ and un-affected by treatment with thapsigargin or caffeine plus ryanodine. Niflumic acid, a Ca²⁺-activated Cl⁻ channel inhibitor, or nifedipine, an L-type Ca²⁺ channel inhibitor, slowed the initial rate of the increase in [Ca²⁺]_i in response to forskolin. Nifedipine did not affect the increase in [Ca²⁺]_i that was slowed by niflumic acid. In Ca²⁺ 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 Ca²⁺ signals are due to Ca²⁺ influx, but not the release of Ca²⁺ from Ca²⁺ stores, and that the initial rapid increase in [Ca²⁺]_i is associated with the activation of the voltage-dependent Ca²⁺ channels in rat ORNs.