title: Afterhyperpolarization current in myenteric neurons of the guinea pig duodenum.
abstract: Whole cell patch and cell-attached recordings were obtained from neurons in intact ganglia of the myenteric plexus of the guinea pig duodenum. Two classes of neuron were identified electrophysiologically: phasically firing AH neurons that had a pronounced slow afterhyperpolarization (AHP) and tonically firing S neurons that lacked a slow AHP. We investigated the properties of the slow AHP and the underlying current (I(AHP)) to address the roles of Ca(2+) entry and Ca(2+) release in the AHP and the characteristics of the K(+) channels that are activated. AH neurons had a resting potential of -54 mV and the AHP, which followed a volley of three suprathreshold depolarizing current pulses delivered at 50 Hz through the pipette, averaged 11 mV at its peak, which occurred 0.5-1 s following the stimulus. The duration of these AHPs averaged 7 s. Under voltage-clamp conditions, I(AHP)'s were recorded at holding potentials of -50 to -65 mV, following brief depolarization of AH neurons (20-100 ms) to positive potentials (+35 to +50 mV). The null potential of the I(AHP) at its peak was -89 mV. The AHP and I(AHP) were largely blocked by omega-conotoxin GVIA (0.6-1 microM). Both events were markedly decreased by caffeine (2-5 mM) and by ryanodine (10-20 microM) added to the bathing solution. Pharmacological suppression of the I(AHP) with TEA (20 mM) or charybdotoxin (50-100 nM) unmasked an early transient inward current at -55 mV following step depolarization that reversed at -34 mV and was inhibited by niflumic acid (50-100 microM). Mean-variance analysis performed on the decay of the I(AHP) revealed that the AHP K(+) channels have a mean chord conductance of ~10 pS, and there are ~4,000 per AH neuron. Spectral analysis showed that the AHP channels have a mean open dwell time of 2.8 ms. Cell-attached patch recordings from AH neurons confirmed that the channels that open following action currents have a small unitary conductance (10-17 pS) and open with a high probability (</=0.5) within the first 2 s following an action potential. These results indicate that the AHP is largely a consequence of Ca(2+) entry through omega-conotoxin GVIA-sensitive Ca(2+) channels during the action potential, Ca(2+)-triggered Ca(2+) release from caffeine-sensitive stores and the opening of Ca(2+)-sensitive small-conductance K(+) channels.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia. F.Vogalis@anatomy.unimelb.edu.au
authors.forename: F
authors.initials: F
authors.lastname: Vogalis
authors.forename: J B
authors.initials: JB
authors.lastname: Furness
authors.forename: W A
authors.initials: WA
authors.lastname: Kunze
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D015640:Ion Channel Gating; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D012433:Ryanodine / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D020864:Calcium Channels, N-Type; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; D012433:Ryanodine; D002110:Caffeine; D009544:Niflumic Acid; D019789:Tetraethylammonium; D020866:omega-Conotoxin GVIA