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A Feltz

Publications and source records attributed to A Feltz.

68 records · Page 4Linked to original sources
PubMed1980

Quinacrine (mepacrine) action at frog end-plate.

1. The effects of quinacrine on end-plate currents (e.p.c.s.), miniature end-plate currents (m.e.p.c.s.) and ionophoretic responses at voltage clamped frog end-plates were investigated. 2. A quinacrine concentration (2 microM) that by itself has little effect on m.p.e.c.s. will considerably attenuate responses to bath applied carbachol. The combined effect of the two drugs causes the m.e.p.c.s. to disappear. 3. The depressant effect of quinacrine on ionophoretic responses to carbachol or acetylcholine is increased in acid solutions and decreased in alkaline solutions, suggesting that quinacrine is active as an acridinium ion. 4. Quinacrine (2-10 microM) causes a use-dependent block of end-plate channels which manifests as an inhibitory effect of an ionophoretic prepulse on the response to a test pulse. The inhibitory interaction decays exponentially with a time constant tau s that depends on the nature of the agonist used for the prepulse, on the quinacrine concentration, and on the membrane potential. 5. Quinacrine (5-20 microM) reduces the amplitude of e.p.c.s. and m.e.p.c.s. It also increases the rate of decay of the e.p.c. or m.e.p.c. tails, which remain exponential. The decay rate constant 1/tau f increases linearly with quinacrine concentration both in the presence and absence of 3 microM-neostigmine. The slope of this linear relation increases slightly with membrane hyperpolarization. 6. These data suggest that quinacrine's main action is a slow, voltage dependent blockade of open end-plate channels, though there are probably additional effects on acetylcholinesterase and channel opening. In accordance with the open channel blocking model, 1/tau s and 1/tau f both increase linearly with quinacrine concentration. However, the slopes of these lines lead to rather different estimates of the forward blocking rate constant (8 X 10(7) and 4 X 10(8) M-1 S-1 respectively). 7. The unblocking rate constant is about 5 S-1 at -80 mV. It is much more voltage dependent than the forward rate constant.

Acetylcholine↗
PubMed1980

End-plate channel opening and the kinetics of quinacrine (mepacrine) block.

1. The effects of quinacrine on the relaxation of the agonist-induced currents in response to a voltage step were investigated at voltage clamped frog end-plates. A fast perfusion technique allowed the application of known concentrations of the agonist acetylcholine (ACh) or carbachol to end-plate viewed with Nomarski optics. 2. In the presence of quinacrine, and in response to a hyperpolarizing voltage jump, an agonist-induced current shows a fast initial relaxational increase and then relaxes slowly back to a new equilibrium level. 3. The slow relaxation can be described by a single exponential with a time constant tau s . tau s gets smaller at increasing quinacrine concentrations (0--2 microM) and the decay rate constant, 1/tau s, increases linearly with quinacrine concentration. Increasing agonist concentration reduces tau s, in a manner dependent on the nature of the agonist. Tau s is markedly lengthened at more hyperpolarized potential, but this voltage effect gets less at higher concentrations of agonist. 4. These data suggest a slow voltage dependent blockage of open end-plate channels by quinacrine. The binding rate constant of quinacrine is estimated as 10(8) M-1 s-1, and the voltage dependent, backward rate constant, as 5 s-1 at -60 mV and 1 s-1 at -140 mV. These values are in fair agreement with those obtained from the analysis presented in the preceding paper. 5. The agonist concentration dependence of the blocking kinetics is compatible with a simple model for channel opening. In this model, independent sequential binding of two agonist molecules leads to an isomerization of the receptor. The intrinsic binding constant of ACh is estimated to be around 20 microM, and for carbachol around 200 microM. Distinct isomerization constants could lead to a maximal activation of 70% of the available channels by ACh, and only 40% by carbachol. 6. An example of a possible interaction in between quinacrine block and desensitization is shown. At the break of an hyperpolarizing jump which has increased quinacrine blockade, a transient increase in the synaptic current is observed with apparently a temporary reduction of the desensitization.

Acetylcholine↗
PubMed1977

Analysis of atropine action at the frog neutromuscular junction.

1. Atropine action on the end-plate currents (e.p.c.s) has been analysed at the macroscopic and elementary levels. 2. The shortening effect of atropine on the e.p.c. and m.e.p.c. level can be fully explained by a reduction of the life time of the elementary current: this effect is markedly increased at more hyperpolarized membrane potentials and at higher concentrations of atropine. 3. It is therefore suggested that atropine binds to the open acetylcholine-receptor complex, leading to a state with a null conductance. According to this model, the forward rate constant of atropine binding could be calculated and was of the order of 10(7) M-1 S-1 AT -90 MV and 20-22 degrees C. 4. Although the conductance at the peak of the e.p.c. is reduced by atropine and becomes voltage sensitive, the elementary conductance is affected neither by voltage nor by atropine. 5. The exclusive binding of atropine to the activated ACh-receptor complex, as proposed above, does not appear to explain this phenomenon. Another binding occurring before the channel is open with a dissociation constant of 60 micrometer could account for this effect.

Animals↗
PubMed1974

Direct estimates of chloride activity in muscle fibres depolarized by carbachol.

Intracellular chloride activities have been measured in muscle fibres with chloride-sensitive electrodes. It was found that the depolarization induced by carbachol produces an influx of chloride ions, the accumulation of which leads to further sustained depolarization. The present study thus confirms the evidence put forward by Jenkinson & Terrar (1973) of an influence of chloride ions on the membrane potential after a prolonged application of carbachol.

Animals↗
PubMed1971

Competitive interaction of beta-guanidino propionic acid and gamma-aminobutyric acid on the muscle fibre of the crayfish.

1. The interaction of beta-guanidino propionic acid and gamma-aminobutyric acid has been investigated on the crayfish muscle by measurement of the membrane conductance.2. The increase in membrane conductance produced by GABA is depressed by beta-guanidino propionic acid. This antagonist acts in a competitive way as shown by the shift of log dose-response curves and by the results of tests for competitive interaction (method of Schild (1947); Lineweaver and Burk's plot).3. Perfusion of GABA was shown to induce a receptor desensitization. As a consequence, the slope of the dose-response curve plotted in Hill's co-ordinates increases when care is taken to minimize this phenomenon. The significance of this slope for establishing the real number of GABA molecules binding with the GABA receptor is discussed.

Aminobutyrates↗
PubMed1971

An analysis of acetylcholine responses of junctional and extrajunctional receptors of frog muscle fibres.

1. An analysis has been made of the distribution and rise time of the responses induced by electrophoretic application of ACh on junctional and extrajunctional receptors of the neuromuscular junction of the frog.2. The junctional and the extrajunctional responses appear to constitute two independent groups with no overlapping characteristics: (a) the responses evoked from junctional receptors show always a high ;sensitivity' (30-100 mV/nC) and a rise time usually shorter than 10 msec that does not lengthen as the ACh dose is increased; (b) the responses evoked from extrajunctional area show a lower sensitivity (0.5-10 mV/nC) and a slow rise time that is a linear function of the dose Q((2/3)) of ACh.3. The lengthening of the rise time of extrajunctional response with increasing doses of ACh is interpreted by supposing that larger doses saturate larger areas of a membrane of low sensitivity uniformly covered with receptors. On the contrary, at junctional spots the does of ACh would be insufficient to saturate the receptors and rise time will be independent of dose.4. Relatively unresponsive zones may exist between junctional spots and extrajunctional areas and between neighbouring extrajunctional areas.5. Extrajunctional areas are subjected to significant seasonal variations; in summer they are practically absent, in autumn they appear as elongated areas of about 20 mu wide and 50 mu long, and late in winter they fuse together and all the ;end-plate' zone becomes sensitive to ACh.

Acetylcholine↗
PubMed1971

Ionic permeability changes induced by some cholinergic agonists on normal and denervated frog muscles.

1. The reversal potential of responses to iontophoretic application of acetylcholine, carbamylcholine and decamethonium has been measured at junctional and extrajunctional sensitive areas of the normal sartorius muscle of the frog.2. The values obtained with any one of the drugs at junctional spots were similar to those previously reported for the end-plate potential (about - 16 mV).3. On the other hand, at extrajunctional areas the reversal potential of responses to these agonists was found to have a mean value of - 42 mV. The muscle-tendon responses to acetylcholine reversed at - 51 mV.4. The response to decamethonium was used to determine the nature of the ionic permeability changes mediated by the extrajunctional receptors. The results obtained show that extrajunctional responses are due to an increase in conductance to Na(+) and K(+) but not to Cl(-).5. The reversal potential of acetylcholine responses in denervated frog sartorius was - 42 mV both at former junctional spots and at non-neural sensitized regions.6. These different values of the reversal potential can be due either to effects of receptor density on the ionic selectivity of the membrane or to regional variations in the extracellular ionic accumulation during the transmitter action.

Acetylcholine↗