Spontaneous recovery from depolarizing drugs in rat diaphragm.

Creese, R.; Mitchell, L.D.

doi:10.1113/jphysiol.1981.sp013657

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…The depolarization produced by carbachol in rat diaphragm is followed by spontaneous recovery in the presence of the drug, and this repolarization has been interpreted in terms of a metabolically driven sodium-potassium transfer pump (Creese & Mitchell, 1981). In the present study the prolonged effects ofdecamethonium have been examined in denervated guinea-pig diaphragm, in which net movements of potassium and subsequent recovery can also be demonstrated.…”

Section: Introductionmentioning

confidence: 95%

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Recovery from decamethonium in rat muscle and denervated guinea‐pig diaphragm.

Creese¹,

Humphrey²,

Mitchell³

1983

The Journal of Physiology

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SUMMARY1. In denervated guinea-pig diaphragm the depolarization produced by decamethonium (100 pM) was followed by an initial phase of recovery, and then by a slow restoration ofmembrane potential in the presence ofthe drug, with hyperpolarization. Membrane potentials were measured by repeated insertions. The slow phase of spontaneous recovery was not found in the absence of potassium or in the presence of ouabain (100/M).2. With 1 /SM-decamethonium the net loss of potassium from denervated muscle was 17 % by wet weight in 20 min as compared with controls, which represents a loss of over 30 mm in internal concentration. Similar results were obtained with 100 FMdecamethonium. Spontaneous recovery of potassium occurred in the succeeding 2 h in the presence of 1 /SM and 100 /SM-decamethonium. With 5 nM-decamethonium muscles exposed for 20 min had a potassium content which was not reduced as compared with controls.3. In rat diaphragm decamethonium (100/M) also produced depolarization and slow spontaneous recovery which was not seen in the absence of potassium or the presence of ouabain. With 3 mM-decamethonium spontaneous recovery of potential was complete in 5 min.4. Change from 5 mM-potassium to potassium-free solution produced consistent hyperpolarization in denervated guinea-pig diaphragm. In rat diaphragm at 38 0C the results were variable, with some fibres showing hyperpolarization while others showed depolarization.

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Section: Introductionmentioning

confidence: 95%

“…Electrical recording. In rat diaphragm the end-plates were localized and the effects of decamethonium were studied by continuous recording and by repeated puncture (Creese & Mitchell, 1981). For denervated guinea-pig diaphragm the strip of muscle was set up horizontally in flowing saline and similar recording methods were used.…”

Section: Introductionmentioning

confidence: 99%

Recovery from decamethonium in rat muscle and denervated guinea‐pig diaphragm.

Creese¹,

Humphrey²,

Mitchell³

1983

The Journal of Physiology

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“…This inconsistency may be explained if the effect of carbachol were to have been limited by desensitization of the endplate cholinoceptors. In our experiments with ECO, m.e.p.ps were present, but the m.e.p.ps of rat diaphragm 'promptly disappeared' in the presence of 10-M carbachol (Creese & Mitchell, 1981), and the endplate current due to carbachol applied to guinea-pig diaphragm declined rapidly over the first 5min (Creese et al, 1987). Furthermore, Bray et al (1982) found that m.e.p.ps were unaffected by 10-7 M carbachol but reduced by 106 M. Thus it is considered that the accumulation of Ca after carbachol was limited by desensitization and the accumulation due to non-quantal release of ACh after ECO was not limited to the same extent.…”

Section: Methodsmentioning

confidence: 91%

Accumulation of extracellular calcium at the endplate of mouse diaphragm after ecothiopate in vitro

Burd

Ferry

Smith

1989

British J Pharmacology

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Experiments were carried out to investigate the accumulation from the extracellular medium of 45Ca2+ by the endplate region of skeletal muscle. Mouse diaphragm muscle was incubated in physiological saline labelled with 45Ca at 37°C for periods of up to 1.5 h. The muscle was divided into junctional and non‐junctional portions and the Ca from the extracellular fluid accumulated at the endplate determined from the 45Ca content of the portions. The accumulation of extracellular Ca at the endplate region of muscles incubated in physiological saline alone was nil, but there was accumulation in the presence of the anticholinesterase ecothiopate iodide 0.5 × 10−6 m (ECO). Stimulation of the phrenic nerve at 0.02 Hz caused no further increase in accumulation, but reduced the amount of spontaneous fasciculation. In tetrodotoxin (TTX) 10−6 m, the accumulation was halved, and in 3.5 mM Mg2+ the accumulation was nil. Carbachol 10−4 m resulted in an accumulation of Ca similar to that in ECO. It is concluded that there was an accumulation of extracellular Ca following excitation of the nerve by stimulation at a low frequency and during the spontaneous fasciculations, and about half of the accumulation of extracellular Ca after ECO in the experiments was due to the postsynaptic action of ACh released non‐quantally from the nerve terminals.

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“…Spontaneous repolarization in rat muscle has been attributed to desensitization plus Na-K pump action stimulated probably by intracellular Na+ gain (Creese & Mitchell, 1981), and similar mechanisms are likely to occur in guinea-pig diaphragm. The carbacholinduced end-plate current inferred from Fig.…”

Section: Spontaneous Repolarization and Pump Actionmentioning

confidence: 99%

“…In rat muscle spontaneous recovery of membrane potential in the presence of depolarizing drugs has been demonstrated by Creese & Mitchell (1981), but their analysis was limited by the necessity to make repeated impalements with microelectrodes. Spontaneous recovery of potential is also found in muscle fibres of guinea-pig diaphragm, with the advantage that in this preparation the fibres are larger and recovery occurs with micro-electrodes in position.…”

Section: Introductionmentioning

confidence: 99%

The role of the sodium pump during prolonged end‐plate currents in guinea‐pig diaphragm.

Creese

Head

Jenkinson

1987

The Journal of Physiology

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SUMMARY1. Depolarization caused by carbachol or decamethonium is followed by spontaneous recovery of membrane potential in the presence of the drug. The involvement of the Na pump in this recovery has been investigated in guinea-pig diaphragm at 37°C.2. Restoration of potassium ions (K+) to the bathing solution gives a rapid recovery of membrane potential which is compatible with a component of recovery of potential being attributable to an electrogenic ion pump and from which a Na pump current of over 60 nA has been estimated.3. The maintenance of membrane potential in the presence of depolarizing drugs is interpreted in terms of a residual rate of channel opening at a time when the membrane potential is restored, balanced by Na pump action producing tubular depletion of K+. To account for these results a Na pump c>onductance has been added to a model circuit of drug action.4. The peak end-plate current produced by carbachol (80 ,UM) is 100 nA (n = 11) as recorded by the voltage clamp technique; similar estimates may be obtained from measurements of input resistance which falls to 31 % of the initial value (n = 5). In muscles desensitized by carbachol for 30 min the end-plate current is 11 nA. 5. In normal muscle removal of K+ from the bathing solution produces a reversible hyperpolarization. In muscles where the membrane potential has recovered in the continued presence of the drug, a hyperpolarization is also found on removal of K+. Withdrawal of K+ during the early stage of spontaneous recovery of potential produces a depolarization or an arrest of the spontaneous repolarization. These results are interpreted in terms of the Na pump producing different effects during the course of spontaneous repolarization.6. Indirect evidence for K+ depletion in the transverse tubules by the Na pump is provided by an increased resistance to inward current following brief exposure to carbachol or decamethonium. A similar mechanism is used to interpret both the observed change in end-plate reversal potential to a more negative value and the marked diminution in the amplitude of the action potential at the end-plate during drug action.

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Spontaneous recovery from depolarizing drugs in rat diaphragm.

Cited by 12 publications

References 31 publications

Recovery from decamethonium in rat muscle and denervated guinea‐pig diaphragm.

Recovery from decamethonium in rat muscle and denervated guinea‐pig diaphragm.

Accumulation of extracellular calcium at the endplate of mouse diaphragm after ecothiopate in vitro

The role of the sodium pump during prolonged end‐plate currents in guinea‐pig diaphragm.

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