Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 355K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kits, K.S. Articles by Veerman, M.J. Search for Related Content PubMed PubMed Citation Articles by Kits, K.S. Articles by Veerman, M.J. Social Bookmarking                            What's this?

Article

From the Graduate School Neurosciences Amsterdam, Research Institute of Neuroscience, Vrije Universiteit, Faculty of Biology, 1081 HV Amsterdam, Netherlands

The neuropeptide Phe-Met-Arg-Phe-amide (FMRFa) dose dependently (ED₅₀ = 23 nM) activated a K⁺ current in the peptidergic caudodorsal neurones that regulate egg laying in the mollusc Lymnaea stagnalis. Under standard conditions ([K⁺]_o = 1.7 mM), only outward current responses occurred. In high K⁺ salines ([K⁺]_o = 20 or 57 mM), current reversal occurred close to the theoretical reversal potential for K⁺. In both salines, no responses were measured below –120 mV. Between –120 mV and the K⁺ reversal potential, currents were inward with maximal amplitudes at –60 mV. Thus, U-shaped current–voltage relations were obtained, implying that the response is voltage dependent. The conductance depended both on membrane potential and extracellular K⁺ concentration. The voltage sensitivity was characterized by an e-fold change in conductance per 14 mV at all [K⁺]_o. Since this result was also obtained in nearly symmetrical K⁺ conditions, it is concluded that channel gating is voltage dependent. In addition, outward rectification occurs in asymmetric K⁺ concentrations. Onset kinetics of the response were slow (rise time 650 ms at –40 mV). However, when FMRFa was applied while holding the cell at –120 mV, to prevent activation of the current but allow activation of the signal transduction pathway, a subsequent step to –40 mV revealed a much more rapid current onset. Thus, onset kinetics are largely determined by steps preceding channel activation. With FMRFa applied at –120 mV, the time constant of activation during the subsequent test pulse decreased from 36 ms at –60 mV to 13 ms at –30 mV, confirming that channel opening is voltage dependent. The current inactivated voltage dependently. The rate and degree of inactivation progressively increased from –120 to –50 mV. The current is blocked by internal tetraethylammonium and by bath- applied 4-aminopyridine, tetraethylammonium, Ba²⁺, and, partially, Cd²⁺ and Cs⁺. The response to FMRFa was affected by intracellular GTPS. The response was inhibited by blockers of phospholipase A₂ and lipoxygenases, but not by a cyclo-oxygenase blocker. Bath-applied arachidonic acid induced a slow outward current and occluded the response to FMRFa. These results suggest that the FMRFa receptor couples via a G-protein to the lipoxygenase pathway of arachidonic acid metabolism. The biophysical and pharmacological properties of this transmitter operated, but voltage-dependent K⁺ current distinguish it from other receptor-driven K⁺ currents such as the S-current- and G-protein-dependent inward rectifiers.

Key Words: Phe-Met-Arg-Phe-amide • S-K current • potassium channel • G-protein • arachidonic acid

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. Scuri, R. Mozzachiodi, and M. Brunelli Role for Calcium Signaling and Arachidonic Acid Metabolites in the Activity-Dependent Increase of AHP Amplitude in Leech T Sensory Neurons J Neurophysiol, August 1, 2005; 94(2): 1066 - 1073. [Abstract] [Full Text] [PDF]

				K. Sasaki, Y. Fujisawa, F. Morishita, O. Matsushima, and Y. Furukawa The enterins inhibit the contractile activity of the anterior aorta of Aplysia kurodai J. Exp. Biol., November 15, 2002; 205(22): 3525 - 3533. [Abstract] [Full Text] [PDF]

				P. Lovell, B. McMahon, and N. I. Syed Synaptic Precedence During Synapse Formation Between Reciprocally Connected Neurons Involves Transmitter-Receptor Interactions and AA Metabolites J Neurophysiol, September 1, 2002; 88(3): 1328 - 1338. [Abstract] [Full Text] [PDF]

				J. R. McDearmid, V. Brezina, and K. R. Weiss AMRP Peptides Modulate a Novel K+ Current in Pleural Sensory Neurons of Aplysia J Neurophysiol, July 1, 2002; 88(1): 323 - 332. [Abstract] [Full Text] [PDF]

				M. K. Graham, I. Fairweather, and J. G. McGeown Second messengers mediating mechanical responses to the FARP GYIRFamide in the fluke Fasciola hepatica Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2000; 279(6): R2089 - R2094. [Abstract] [Full Text] [PDF]

				H. van Tol-Steye, J. C. Lodder, H. D. Mansvelder, R. J. Planta, H. van Heerikhuizen, and K. S. Kits Roles of G-Protein beta gamma , Arachidonic Acid, and Phosphorylation in Convergent Activation of an S-Like Potassium Conductance by Dopamine, Ala-Pro-Gly-Trp-NH2, and Phe-Met-Arg-Phe-NH2 J. Neurosci., May 15, 1999; 19(10): 3739 - 3751. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents