Ca²(+) /calmodulin-dependent protein kinase II mediates the octopamine-induced increase in sensitivity in spider VS-3 mechanosensory neurons.

G-protein-coupled octopamine (OA) receptors mediate their effects by Ca²(+) signaling or adjusting intracellular cAMP levels. Depending on OA concentration and cell type, activation of OA receptors in excitable cells triggers excitatory or inhibitory effects, but the mechanisms by which Ca²(+) or cAMP mediates these effects are not well understood. We investigated signaling mechanisms that are potentially activated by OA, and OA effects on excitability and frequency sensitivity in mechanosensory neurons innervating the VS-3 slit sensilla on the patella of the spider Cupiennius salei. These neurons are directly innervated by octopaminergic efferents, and possess OA receptors that were immunoreactive to an antibody against an OA receptor highly expressed in mushroom bodies. OA application enhanced VS-3 neuron sensitivity, especially at high stimulation frequencies. This enhancement lasted for at least 1 h after OA application. Changes in sensitivity were also detected when the Ca²(+) ionophore ionomycin or the cAMP analog 8-Br-cAMP was applied. However, the cAMP pathway was unlikely to mediate the OA effect, as the protein kinase A inhibitor RP-cAMPS did not diminish this effect. In contrast, the OA-induced sensitivity enhancement was significantly reduced by KN-62, an inhibitor of Ca²(+) /calmodulin-dependent protein kinase II (CaMKII), and by the Ca²(+) chelator BAPTA-AM. OA depolarized the neurons by 3.8 mV from resting potential, well below the threshold for opening of voltage-activated Ca²(+) channels. OA also reduced the amplitudes of voltage-activated K(+) currents. We propose that OA receptors in VS-3 neurons activate inositol 1,4,5-trisphosphate, leading to Ca²(+) release from intracellular stores. The Ca²(+) surge switches on CaMKII, which modulates voltage-activated K(+) channels, resulting in persistent enhancement in excitability.