Voltage clamp analysis of acetylcholine produced end‐plate current fluctuations at frog neuromuscular junction

Anderson, C. R.; Stevens, Charles F.

doi:10.1113/jphysiol.1973.sp010410

Cited by 958 publications

(793 citation statements)

References 29 publications

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“…In particular tubocurarine shows strong selectivity in blocking the slow component, whereas hexamethonium more strongly affects the fast component. In this study we have investigated the selectivity of agonists in activating these two components, using the analysis of membrane current noise (Katz & Miledi, 1972; Anderson & Stevens, 1973) to distinguish the contributions of the two types of receptor to the overall membrane response. A noise spectrum consisting of two components can be represented by the equation:…”

Section: Introductionmentioning

confidence: 99%

Analysis of current noise evoked by nicotinic agonists in rat submandibular ganglion neurones

Gray

Rang

1983

British J Pharmacology

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1The kinetics of the responses of rat submandibular ganglion neurones to nicotinic agonists were investigated by the analysis of agonist-induced membrane current noise. 2 Two kinetic components are found in the responses of these cells to acetylcholine, carbachol, suberyldicholine, dimethyl-4-phenylpiperazinium and nicotine, in agreement with previous findings of two components in evoked synaptic currents in these cells. 3 Small, though significant, differences in the relative amplitudes of the two kinetic components were observed in the spectra of noise evoked by the different agonists. In particular, the fast component in the response to carbachol was relatively larger with respect to the slow component than with any other agonist tested. 4 No measurable dependence of the relative sizes of the two components on agonist concentration or membrane potential was observed. 5The evidence supports the hypothesis that the two kinetic components are the product of two independent channel populations for which the agonists tested show some slight differences in selectivity.

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Section: Introductionmentioning

confidence: 99%

Analysis of current noise evoked by nicotinic agonists in rat submandibular ganglion neurones

Gray

Rang

1983

British J Pharmacology

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“…This approach has been limited to a few record patterns including: single opening with or without latency to first opening, where the macroscopic current has been formulated in terms of the distributions of latency to first opening and open duration [3,10,11]; multiple openings without latency to first opening, where the time constants of the macroscopic current were found to correspond approximately to the time constants of the distributions of open duration and burst length [12]; a general case where the relationship has been formulated in terms of the distribution of latency to first opening and a conditioned form of the macroscopic current [10]. In this paper, we have formulated the macroscopic current solely in terms of statistical properties of single channel records for the general case, with the assumption that the channel open duration is independent of the time when the opening has occurred, an assumption that is applicable to many channels.…”

Section: Discussion Relating Macroscopic Current To Channel Statisticsmentioning

confidence: 99%

“…It has been reported that for this case, the life time of open duration (with a single exponential distribution) is equal to the time constant of an exponentially decaying macroscopic current [11,23]. Here H(t) will be a Dirac delta function as all the openings occur at time zero:…”

Section: Explaining Previous Observationsmentioning

confidence: 99%

“…The macroscopic current can be calculated in terms of transition-rates between kinetic states of a known Markov model of the channel gating [5], or directly from the statistical properties of single channel records. The second approach does not require knowledge of the underlying stochastic process of channel gating [3,[10][11][12] and is the approach taken in this study.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between the macroscopic current and single channel records was first explained by Anderson and Stevens [11]. They assumed that all channels open simultaneously (single opening) with an exponentially distributed open duration and showed that the life time of open duration is equal to the time constant of the exponentially decaying macroscopic current.…”

Section: Introductionmentioning

confidence: 99%

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Statistical properties of ion channel records. Part I: Relationship to the macroscopic current

Nekouzadeh

Rudy

2007

Mathematical Biosciences

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Macroscopic ion channel current can be derived by summation of the stochastic records of individual channel currents. In this paper we present two probability density functions of single channel records that can uniquely determine the macroscopic current regardless of other statistical properties of records or the stochastic model of channel gating (presented often with stationary Markov models). We show that H(t), probability density function of channel opening events (introduced explicitly in this paper), and D(t), probability density function of the open duration (sometimes has named dwell time distribution as well), determine the normalized macroscopic current, G(t), through: where P(t) is the cumulative density function of H(t), Q(t) is the cumulative density function of D (t), * is the symbol of convolution integral and G(t) is the macroscopic current divided by the amplitude of single channel current and the number of single channel sweeps.Compared to other equations for the macroscopic current, here the macroscopic current is expressed only in terms of the statistical properties of single channel current and not the stochastic model of ion channel gating or a conditioned form of macroscopic current.Single channel currents of an inactivating BK channel were used to validate this relationship experimentally too. In this paper we used median filters as they can remove the unwanted noise without smoothing the transitions between open and closed states (compare to low pass filters). This filtering leads to more accurate measurement of transition times and less amount of missed events.

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A transgenic mouse model of the slow-channel syndrome

et al. 1996

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To investigate the effect of acetylcholine receptor (AChR) mutations on neuromuscular transmission and to develop a model for the human neuromuscular disease, the slow‐channel syndrome, we generated transgenic mice with abnormal AChRs using a δ subunit with a mutation in the ion channel domain. In three transgenic lines, nerve‐evoked end‐plate currents and spontaneous miniature end‐plate currents (MEPCs) had prolonged decay phases and MEPC amplitudes were reduced by 33%. Single nerve stimuli elicited repetitive compound muscle action potentials in vivo. Transgenic mice were abnormally sensitive to the neuromuscular blocker, curare. These observations demonstrate that we can predictably alter AChR function, synaptic responses, and muscle fiber excitation in vivo by overexpressing subunits containing well‐defined mutations. Furthermore, these data support the hypothesis that the electrophysiological findings in the neuromuscular disorder, the slow‐channel syndrome, are due to mutant AChRs. © 1996 John Wiley & Sons, Inc.

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Voltage clamp analysis of acetylcholine produced end‐plate current fluctuations at frog neuromuscular junction

Cited by 958 publications

References 29 publications

Analysis of current noise evoked by nicotinic agonists in rat submandibular ganglion neurones

Analysis of current noise evoked by nicotinic agonists in rat submandibular ganglion neurones

Statistical properties of ion channel records. Part I: Relationship to the macroscopic current

A transgenic mouse model of the slow-channel syndrome

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