Non-stationary fluctuations of the potassium conductance at the node of Ranvier of the frog

F. Conti, B. Hille, W. Nonner

Research output: Contribution to journalArticle

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Abstract

1. Potassium currents were recorded from voltage-clamped nodes of isolated, myelinated axons of Rana pipiens. Nodes were maintained in a modified Ringer solution containing tetrodotoxin to block sodium current and 47.5 mM-potassium to minimize effects of extracellular potassium accumulation. Voltage protocols included depolarizing pulses lasting a few milliseconds to several seconds. Fluctuations about the ensemble average of the current were characterized in terms of non-stationary variance and autocovariance. 2. The fluctuations had a Gaussian amplitude distribution and were virtually free of contaminations from systematic variations of the membrane current. Corrections for background noise were based on measurements done while potassium current was blocked with tetraethylammonium, and on simulations of extrinsic current fluctuations expected to arise from noise in the actual membrane voltage. 3. The fluctuations were attributed to variations of nodal potassium conductance, since they were absent at the reversal potential of the potassium current and at membrane voltages that do not activate potassium current. Covariances indicated that voltage steps that reversed a macroscopic potassium current also reversed the sign of the fluctuation. 4. Plots of the conductance variance versus the mean potassium conductance were generated from both the activation and deactivation (tail) phases of the potassium currents at various voltages between -80 and +70 mV. When the current was activated by a small depolarization (-50 mV) the trajectories from both phases were indistinguishable and were fitted by the parabola expected for a single population of channels with only one open-channel conductance. Apparent single-channel conductance from the early activation phase averaged 24 pS and was not significantly voltage dependent. 5. In contrast, experiments with large depolarizations (+10 to +70 mV) gave significantly different variance-mean trajectories during activation and deactivation and these trajectories were poorly fitted by parabolae. This result indicates that the fluctuations reflect several populations of channels and/or a population of channels that can have several levels of non-zero conductance. 6. Projections of the fluctuation covariance showed long correlations, as well as the rapidly decaying component expected from the activation gating of channels. A slow fluctuation arose at a time slightly later than the rise of potassium current, spanned the entire length of brief depolarizations, and extended up to 880 ms during long depolarizations. The early onset of this slow fluctuation indicates that it is not due to slow turn-on of a population of 'slow' potassium channels. Rather it is consistent with the presence of a slow modulatory process that alters the activity of rapidly activating potassium channels. 7. Experiments that activated large potassium conductances revealed a negative correlation between the conductance fluctuations during the onset of the current and those during the stationary or tail phases of the current. The negative correlation requires that channels can exist in at least two conducting forms and that these forms interconvert slowly during the 2-5 s intervals between successive recordings. 8. The results were fitted by a model incorporating two interconverting forms of potassium channel. One form can be activated to carry a steady potassium current and has a single-channel conductance of 13 pS. The second form (represented on average by 20 out of 100 channels) is activated at a rate similar to that of the first form, but then rapidly inactivates; its open conductance is higher (60 pS).

Original languageEnglish
Pages (from-to)199-230
Number of pages32
JournalJournal of Physiology
VolumeVOL. 353
StatePublished - Jan 1 1984
Externally publishedYes

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Ranvier's Nodes
Anura
Potassium
Potassium Channels
Population
Membranes
Noise
Rana pipiens
Tetraethylammonium
Normal Distribution
Tetrodotoxin

ASJC Scopus subject areas

  • Physiology

Cite this

Non-stationary fluctuations of the potassium conductance at the node of Ranvier of the frog. / Conti, F.; Hille, B.; Nonner, W.

In: Journal of Physiology, Vol. VOL. 353, 01.01.1984, p. 199-230.

Research output: Contribution to journalArticle

Conti, F. ; Hille, B. ; Nonner, W. / Non-stationary fluctuations of the potassium conductance at the node of Ranvier of the frog. In: Journal of Physiology. 1984 ; Vol. VOL. 353. pp. 199-230.
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abstract = "1. Potassium currents were recorded from voltage-clamped nodes of isolated, myelinated axons of Rana pipiens. Nodes were maintained in a modified Ringer solution containing tetrodotoxin to block sodium current and 47.5 mM-potassium to minimize effects of extracellular potassium accumulation. Voltage protocols included depolarizing pulses lasting a few milliseconds to several seconds. Fluctuations about the ensemble average of the current were characterized in terms of non-stationary variance and autocovariance. 2. The fluctuations had a Gaussian amplitude distribution and were virtually free of contaminations from systematic variations of the membrane current. Corrections for background noise were based on measurements done while potassium current was blocked with tetraethylammonium, and on simulations of extrinsic current fluctuations expected to arise from noise in the actual membrane voltage. 3. The fluctuations were attributed to variations of nodal potassium conductance, since they were absent at the reversal potential of the potassium current and at membrane voltages that do not activate potassium current. Covariances indicated that voltage steps that reversed a macroscopic potassium current also reversed the sign of the fluctuation. 4. Plots of the conductance variance versus the mean potassium conductance were generated from both the activation and deactivation (tail) phases of the potassium currents at various voltages between -80 and +70 mV. When the current was activated by a small depolarization (-50 mV) the trajectories from both phases were indistinguishable and were fitted by the parabola expected for a single population of channels with only one open-channel conductance. Apparent single-channel conductance from the early activation phase averaged 24 pS and was not significantly voltage dependent. 5. In contrast, experiments with large depolarizations (+10 to +70 mV) gave significantly different variance-mean trajectories during activation and deactivation and these trajectories were poorly fitted by parabolae. This result indicates that the fluctuations reflect several populations of channels and/or a population of channels that can have several levels of non-zero conductance. 6. Projections of the fluctuation covariance showed long correlations, as well as the rapidly decaying component expected from the activation gating of channels. A slow fluctuation arose at a time slightly later than the rise of potassium current, spanned the entire length of brief depolarizations, and extended up to 880 ms during long depolarizations. The early onset of this slow fluctuation indicates that it is not due to slow turn-on of a population of 'slow' potassium channels. Rather it is consistent with the presence of a slow modulatory process that alters the activity of rapidly activating potassium channels. 7. Experiments that activated large potassium conductances revealed a negative correlation between the conductance fluctuations during the onset of the current and those during the stationary or tail phases of the current. The negative correlation requires that channels can exist in at least two conducting forms and that these forms interconvert slowly during the 2-5 s intervals between successive recordings. 8. The results were fitted by a model incorporating two interconverting forms of potassium channel. One form can be activated to carry a steady potassium current and has a single-channel conductance of 13 pS. The second form (represented on average by 20 out of 100 channels) is activated at a rate similar to that of the first form, but then rapidly inactivates; its open conductance is higher (60 pS).",
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N2 - 1. Potassium currents were recorded from voltage-clamped nodes of isolated, myelinated axons of Rana pipiens. Nodes were maintained in a modified Ringer solution containing tetrodotoxin to block sodium current and 47.5 mM-potassium to minimize effects of extracellular potassium accumulation. Voltage protocols included depolarizing pulses lasting a few milliseconds to several seconds. Fluctuations about the ensemble average of the current were characterized in terms of non-stationary variance and autocovariance. 2. The fluctuations had a Gaussian amplitude distribution and were virtually free of contaminations from systematic variations of the membrane current. Corrections for background noise were based on measurements done while potassium current was blocked with tetraethylammonium, and on simulations of extrinsic current fluctuations expected to arise from noise in the actual membrane voltage. 3. The fluctuations were attributed to variations of nodal potassium conductance, since they were absent at the reversal potential of the potassium current and at membrane voltages that do not activate potassium current. Covariances indicated that voltage steps that reversed a macroscopic potassium current also reversed the sign of the fluctuation. 4. Plots of the conductance variance versus the mean potassium conductance were generated from both the activation and deactivation (tail) phases of the potassium currents at various voltages between -80 and +70 mV. When the current was activated by a small depolarization (-50 mV) the trajectories from both phases were indistinguishable and were fitted by the parabola expected for a single population of channels with only one open-channel conductance. Apparent single-channel conductance from the early activation phase averaged 24 pS and was not significantly voltage dependent. 5. In contrast, experiments with large depolarizations (+10 to +70 mV) gave significantly different variance-mean trajectories during activation and deactivation and these trajectories were poorly fitted by parabolae. This result indicates that the fluctuations reflect several populations of channels and/or a population of channels that can have several levels of non-zero conductance. 6. Projections of the fluctuation covariance showed long correlations, as well as the rapidly decaying component expected from the activation gating of channels. A slow fluctuation arose at a time slightly later than the rise of potassium current, spanned the entire length of brief depolarizations, and extended up to 880 ms during long depolarizations. The early onset of this slow fluctuation indicates that it is not due to slow turn-on of a population of 'slow' potassium channels. Rather it is consistent with the presence of a slow modulatory process that alters the activity of rapidly activating potassium channels. 7. Experiments that activated large potassium conductances revealed a negative correlation between the conductance fluctuations during the onset of the current and those during the stationary or tail phases of the current. The negative correlation requires that channels can exist in at least two conducting forms and that these forms interconvert slowly during the 2-5 s intervals between successive recordings. 8. The results were fitted by a model incorporating two interconverting forms of potassium channel. One form can be activated to carry a steady potassium current and has a single-channel conductance of 13 pS. The second form (represented on average by 20 out of 100 channels) is activated at a rate similar to that of the first form, but then rapidly inactivates; its open conductance is higher (60 pS).

AB - 1. Potassium currents were recorded from voltage-clamped nodes of isolated, myelinated axons of Rana pipiens. Nodes were maintained in a modified Ringer solution containing tetrodotoxin to block sodium current and 47.5 mM-potassium to minimize effects of extracellular potassium accumulation. Voltage protocols included depolarizing pulses lasting a few milliseconds to several seconds. Fluctuations about the ensemble average of the current were characterized in terms of non-stationary variance and autocovariance. 2. The fluctuations had a Gaussian amplitude distribution and were virtually free of contaminations from systematic variations of the membrane current. Corrections for background noise were based on measurements done while potassium current was blocked with tetraethylammonium, and on simulations of extrinsic current fluctuations expected to arise from noise in the actual membrane voltage. 3. The fluctuations were attributed to variations of nodal potassium conductance, since they were absent at the reversal potential of the potassium current and at membrane voltages that do not activate potassium current. Covariances indicated that voltage steps that reversed a macroscopic potassium current also reversed the sign of the fluctuation. 4. Plots of the conductance variance versus the mean potassium conductance were generated from both the activation and deactivation (tail) phases of the potassium currents at various voltages between -80 and +70 mV. When the current was activated by a small depolarization (-50 mV) the trajectories from both phases were indistinguishable and were fitted by the parabola expected for a single population of channels with only one open-channel conductance. Apparent single-channel conductance from the early activation phase averaged 24 pS and was not significantly voltage dependent. 5. In contrast, experiments with large depolarizations (+10 to +70 mV) gave significantly different variance-mean trajectories during activation and deactivation and these trajectories were poorly fitted by parabolae. This result indicates that the fluctuations reflect several populations of channels and/or a population of channels that can have several levels of non-zero conductance. 6. Projections of the fluctuation covariance showed long correlations, as well as the rapidly decaying component expected from the activation gating of channels. A slow fluctuation arose at a time slightly later than the rise of potassium current, spanned the entire length of brief depolarizations, and extended up to 880 ms during long depolarizations. The early onset of this slow fluctuation indicates that it is not due to slow turn-on of a population of 'slow' potassium channels. Rather it is consistent with the presence of a slow modulatory process that alters the activity of rapidly activating potassium channels. 7. Experiments that activated large potassium conductances revealed a negative correlation between the conductance fluctuations during the onset of the current and those during the stationary or tail phases of the current. The negative correlation requires that channels can exist in at least two conducting forms and that these forms interconvert slowly during the 2-5 s intervals between successive recordings. 8. The results were fitted by a model incorporating two interconverting forms of potassium channel. One form can be activated to carry a steady potassium current and has a single-channel conductance of 13 pS. The second form (represented on average by 20 out of 100 channels) is activated at a rate similar to that of the first form, but then rapidly inactivates; its open conductance is higher (60 pS).

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