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

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 Ca -dependent K current I and the sensitive pheromone-dependent K current I , which both express fast kinetics, were inhibited by 8bcGMP, while a slow K current, I , was activated by 8bcGMP. Furthermore, application of 8bcAMP blocked slowly activating, zero mV-reversing, non-specific cation currents, I and I , 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 Ca levels voltage- and I -dependently. Twenty minutes after application, 8bcGMP blocked a TEA-independent K current, I , and a fast cation current, I , 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 Ca levels. In contrast, adaptation is supported via cGMP, which antagonizes cAMP, opening Ca -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.