Cyclic nucleotide-dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest...

Olfactory receptor neurons (ORNs) of the hawkmoth Manduca sexta sensitize via cAMP- and adapt via cGMP-dependent mechanisms. Perforated patch clamp recordings distinguished 11 currents in these ORNs. Derivatives of cAMP and/or cGMP antagonistically affected three of five K⁺ currents and two non-specific cation currents. The Ca²⁺ -dependent K⁺ current I_K(Ca²⁺₎ and the sensitive pheromone-dependent K⁺ current I_K(cGMP-) , which both express fast kinetics, were inhibited by 8bcGMP, while a slow K⁺ current, I_K(cGMP+) , was activated by 8bcGMP. Furthermore, application of 8bcAMP blocked slowly activating, zero mV-reversing, non-specific cation currents, I_LL and I_cat(PKC?) , which remained activated in the presence of 8bcGMP. Their activations pull the membrane potential towards their 0-mV reversal potentials, in addition to increasing intracellular Ca²⁺ levels voltage- and I_LL -dependently. Twenty minutes after application, 8bcGMP blocked a TEA-independent K⁺ current, I_K(noTEA) , and a fast cation current, I_cat(nRP) , which both shift the membrane potential to negative values. We conclude that conditions of sensitization are maintained at high levels of cAMP, via specific opening/closure of ion channels that allow for fast kinetics, hyperpolarized membrane potentials, and low intracellular Ca²⁺ levels. In contrast, adaptation is supported via cGMP, which antagonizes cAMP, opening Ca²⁺ -permeable channels with slow kinetics that stabilize depolarized resting potentials. The antagonistic modulation of peripheral sensory neurons by cAMP or cGMP is reminiscent of pull-push mechanisms of neuromodulation at central synapses underlying metaplasticity.