Modulation by cGMP of the voltage-gated currents in newt olfactory receptor cells

Effects of cGMP on voltage-gated currents in the somatic membrane of isolat ed newt olfactory receptor cells were investigated using the whole-cell mod e of the patch-clamp technique. Under voltage clamp, membrane depolarizatio n generated time- and voltage-dependent current responses, a transient inwa rd current and a sustained outward current. When cGMP or a membrane permean t analog of cGMP, 8-p-chlorophenylthio-cGMP (CPT-cGMP), was applied to the recorded cell, the amplitude of the transient inward current increased mark edly, but that of the sustained outward current did not change significantl y. When each current was isolated by pharmacological agents, 0.1 mM CPT-cGM P increased the peak amplitude of a Na+ current (I-Na) by similar to 40%, a T-type Ca2+ current (I-Ca,(T)) by similar to 40%, and an L-type Ca2+ curre nt (I-Ca,I-L) by similar to 10%; however it did not change significantly th e amplitude of a delayed rectifier K+ current (I,). A selective cGMP-depend ent protein kinase inhibitor, KT5823, blocked the enhancement by cGMP of I- Na and I-Ca,I-T suggesting that cGMP increases these currents via cGMP-depe ndent phosphorylation. Under current-clamp conditions, application of CPT-c GMP lowered the current threshold of action potentials induced by current i njection, and increased the maximum spike frequency in response to strong s timuli. We suggest that cGMP may lower the threshold in olfactory perceptio n by decreasing the current threshold to generate spikes, and also prevent the saturation of odor signals by increasing the maximum spike frequency. ( C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. Al l rights reserved.