Kinetic analysis of cAMP-activated Na+ current in the molluscan neuron: A diffusion-reaction model

Rong Chi Huang, Rhanor Gillette

Research output: Contribution to journalArticle

Abstract

cAMP-activated Na+ current (INa, cAMP) was studied in voltage-clamped neurons of the seaslug Pleurobranchaea califomica. The current response to injected cAMP varied in both time course and amplitude as the tip of an intracellular injection electrode was moved from the periphery to the center of the neuron soma. The latency from injection to peak response was dependent on the amount of cAMP injected unless the electrode was centered within the cell. Decay of the INa, cAMP response was slowed by phosphodiesterase inhibition. These observations suggest that the kinetics of the INa, cAMP response are governed by cAMP diffusion and degradation. Phosphodiesterase inhibition induced a persistent inward current. At lower concentrations of inhibitor, INa, cAMP response amplitude increased as expected for decreased hydrolysis rate of injected cAMP. Higher inhibitor concentrations decreased INa, cAMP response amplitude, suggesting that inhibitor-induced increase in native cAMP increased basal INa, cAMP and thus caused partial saturation of the current. The Hill coefficient estimated from the plot of injected cAMP to INa, cAMP response amplitude was close to 1.0. An equation modeling INa, cAMP incorporated terms for diffusion and degradation. In it, the first-order rate constant of phosphodiesterase activity was taken as the rate constant of the exponential decay of the /NacAMP response. The stoichiometry of INa, cAMP activation was inferred from the Hill coefficient as 1 cAMP/channel. The equation closely fitted the INa, cAMP response and simulated changes in the waveform of the response induced by phosphodiesterase inhibition. With modifications to accommodate asymmetric INa, cAMP activation, the equation also simulated effects of eccentric electrode position. The simple reaction-diffusion model of the kinetics of INa, cAMP may provide a useful conceptual framework within which to investigate the modulation of INa, cAMP by neuromodulators, intracellular regulatory factors, and pharmacological agents.

Original languageEnglish (US)
Pages (from-to)835-848
Number of pages14
JournalJournal of General Physiology
Volume98
Issue number4
DOIs
StatePublished - Oct 1 1991

Fingerprint

Phosphoric Diester Hydrolases
Neurons
Electrodes
Pleurobranchaea
Injections
Carisoprodol
Neurotransmitter Agents
Hydrolysis
Pharmacology

ASJC Scopus subject areas

  • Physiology

Cite this

Kinetic analysis of cAMP-activated Na+ current in the molluscan neuron : A diffusion-reaction model. / Huang, Rong Chi; Gillette, Rhanor.

In: Journal of General Physiology, Vol. 98, No. 4, 01.10.1991, p. 835-848.

Research output: Contribution to journalArticle

@article{75c4f7ed9ecd4d58aeb41ac82d8bf4a3,
title = "Kinetic analysis of cAMP-activated Na+ current in the molluscan neuron: A diffusion-reaction model",
abstract = "cAMP-activated Na+ current (INa, cAMP) was studied in voltage-clamped neurons of the seaslug Pleurobranchaea califomica. The current response to injected cAMP varied in both time course and amplitude as the tip of an intracellular injection electrode was moved from the periphery to the center of the neuron soma. The latency from injection to peak response was dependent on the amount of cAMP injected unless the electrode was centered within the cell. Decay of the INa, cAMP response was slowed by phosphodiesterase inhibition. These observations suggest that the kinetics of the INa, cAMP response are governed by cAMP diffusion and degradation. Phosphodiesterase inhibition induced a persistent inward current. At lower concentrations of inhibitor, INa, cAMP response amplitude increased as expected for decreased hydrolysis rate of injected cAMP. Higher inhibitor concentrations decreased INa, cAMP response amplitude, suggesting that inhibitor-induced increase in native cAMP increased basal INa, cAMP and thus caused partial saturation of the current. The Hill coefficient estimated from the plot of injected cAMP to INa, cAMP response amplitude was close to 1.0. An equation modeling INa, cAMP incorporated terms for diffusion and degradation. In it, the first-order rate constant of phosphodiesterase activity was taken as the rate constant of the exponential decay of the /NacAMP response. The stoichiometry of INa, cAMP activation was inferred from the Hill coefficient as 1 cAMP/channel. The equation closely fitted the INa, cAMP response and simulated changes in the waveform of the response induced by phosphodiesterase inhibition. With modifications to accommodate asymmetric INa, cAMP activation, the equation also simulated effects of eccentric electrode position. The simple reaction-diffusion model of the kinetics of INa, cAMP may provide a useful conceptual framework within which to investigate the modulation of INa, cAMP by neuromodulators, intracellular regulatory factors, and pharmacological agents.",
author = "Huang, {Rong Chi} and Rhanor Gillette",
year = "1991",
month = "10",
day = "1",
doi = "10.1085/jgp.98.4.835",
language = "English (US)",
volume = "98",
pages = "835--848",
journal = "Journal of General Physiology",
issn = "0022-1295",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Kinetic analysis of cAMP-activated Na+ current in the molluscan neuron

T2 - A diffusion-reaction model

AU - Huang, Rong Chi

AU - Gillette, Rhanor

PY - 1991/10/1

Y1 - 1991/10/1

N2 - cAMP-activated Na+ current (INa, cAMP) was studied in voltage-clamped neurons of the seaslug Pleurobranchaea califomica. The current response to injected cAMP varied in both time course and amplitude as the tip of an intracellular injection electrode was moved from the periphery to the center of the neuron soma. The latency from injection to peak response was dependent on the amount of cAMP injected unless the electrode was centered within the cell. Decay of the INa, cAMP response was slowed by phosphodiesterase inhibition. These observations suggest that the kinetics of the INa, cAMP response are governed by cAMP diffusion and degradation. Phosphodiesterase inhibition induced a persistent inward current. At lower concentrations of inhibitor, INa, cAMP response amplitude increased as expected for decreased hydrolysis rate of injected cAMP. Higher inhibitor concentrations decreased INa, cAMP response amplitude, suggesting that inhibitor-induced increase in native cAMP increased basal INa, cAMP and thus caused partial saturation of the current. The Hill coefficient estimated from the plot of injected cAMP to INa, cAMP response amplitude was close to 1.0. An equation modeling INa, cAMP incorporated terms for diffusion and degradation. In it, the first-order rate constant of phosphodiesterase activity was taken as the rate constant of the exponential decay of the /NacAMP response. The stoichiometry of INa, cAMP activation was inferred from the Hill coefficient as 1 cAMP/channel. The equation closely fitted the INa, cAMP response and simulated changes in the waveform of the response induced by phosphodiesterase inhibition. With modifications to accommodate asymmetric INa, cAMP activation, the equation also simulated effects of eccentric electrode position. The simple reaction-diffusion model of the kinetics of INa, cAMP may provide a useful conceptual framework within which to investigate the modulation of INa, cAMP by neuromodulators, intracellular regulatory factors, and pharmacological agents.

AB - cAMP-activated Na+ current (INa, cAMP) was studied in voltage-clamped neurons of the seaslug Pleurobranchaea califomica. The current response to injected cAMP varied in both time course and amplitude as the tip of an intracellular injection electrode was moved from the periphery to the center of the neuron soma. The latency from injection to peak response was dependent on the amount of cAMP injected unless the electrode was centered within the cell. Decay of the INa, cAMP response was slowed by phosphodiesterase inhibition. These observations suggest that the kinetics of the INa, cAMP response are governed by cAMP diffusion and degradation. Phosphodiesterase inhibition induced a persistent inward current. At lower concentrations of inhibitor, INa, cAMP response amplitude increased as expected for decreased hydrolysis rate of injected cAMP. Higher inhibitor concentrations decreased INa, cAMP response amplitude, suggesting that inhibitor-induced increase in native cAMP increased basal INa, cAMP and thus caused partial saturation of the current. The Hill coefficient estimated from the plot of injected cAMP to INa, cAMP response amplitude was close to 1.0. An equation modeling INa, cAMP incorporated terms for diffusion and degradation. In it, the first-order rate constant of phosphodiesterase activity was taken as the rate constant of the exponential decay of the /NacAMP response. The stoichiometry of INa, cAMP activation was inferred from the Hill coefficient as 1 cAMP/channel. The equation closely fitted the INa, cAMP response and simulated changes in the waveform of the response induced by phosphodiesterase inhibition. With modifications to accommodate asymmetric INa, cAMP activation, the equation also simulated effects of eccentric electrode position. The simple reaction-diffusion model of the kinetics of INa, cAMP may provide a useful conceptual framework within which to investigate the modulation of INa, cAMP by neuromodulators, intracellular regulatory factors, and pharmacological agents.

UR - http://www.scopus.com/inward/record.url?scp=0026318881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026318881&partnerID=8YFLogxK

U2 - 10.1085/jgp.98.4.835

DO - 10.1085/jgp.98.4.835

M3 - Article

C2 - 1720449

AN - SCOPUS:0026318881

VL - 98

SP - 835

EP - 848

JO - Journal of General Physiology

JF - Journal of General Physiology

SN - 0022-1295

IS - 4

ER -