RT Journal Article SR Electronic T1 Cyclic Nucleotide-Gated Channels Contribute to the Cholinergic Plateau Potential in Hippocampal CA1 Pyramidal Neurons JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8707 OP 8714 DO 10.1523/JNEUROSCI.21-22-08707.2001 VO 21 IS 22 A1 J. Brent Kuzmiski A1 Brian A. MacVicar YR 2001 UL http://www.jneurosci.org/content/21/22/8707.abstract AB Plateau potentials are prolonged membrane depolarizations that are observed in hippocampal pyramidal neurons when spiking and Ca2+ entry occur in combination with muscarinic receptor activation. In this study, we used whole-cell voltage clamping to study the current underlying the plateau potential and to determine the cellular signaling pathways contributing to this current. When combined with muscarinic stimulation, depolarizing command potentials that evoked Ca2+ influx elicited a prolonged tail current (Itail) that had an extrapolated reversal potential of −20 mV.Itail was not observed when intracellular Ca2+ levels were chelated with 10 mmintracellular BAPTA, and Itail was reversibly depressed in low external sodium. WhenItail was evoked at intervals >3 min, current amplitudes were stable for up to 1 hr. However, at shorter intervals, Itail was refractory, with a time constant of recovery of 43.5 sec. The inhibitors of soluble guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and 6-anilino-5,8-quinolinequinone depressedItail and zaprinast, which blocks cGMP-specific phosphodiesterase, enhancedItail, suggesting that a component ofItail was activated by cGMP. The inhibitors of cyclic nucleotide-gated (CNG) channelsl-cis-diltiazem and 2′,4′-dichlorobenzamil reversibly depressed Itail. However, protein kinase G inhibition had no effect. Therefore, these results indicate that a component of Itail is attributable to activation of CNG channels. We conclude that Ca2+ influx when combined with muscarinic receptor activation activates soluble guanylate cyclase and increases cGMP levels. The increased cGMP activates CNG channels and leads to prolonged depolarization. The cation conductance of the CNG channel contributes to the prolonged depolarization of the plateau potential.