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Y Lass

Publications and source records attributed to Y Lass.

At least 37 records · Page 2Linked to original sources
PubMed1983

Evidence for acetylcholine receptor blockade by intracellular hydrogen ions in cultured chick myoballs.

Acetylcholine (ACh)-induced membrane currents were recorded in voltage-clamped myoballs in culture. The ACh sensitivity and the charge transfer per channel (Qc) were doubled in NH4+ at normal extracellular pH (pHo). Immediately after wash-out of NH4+, the ACh sensitivity and Qc undershot below the control. The recovery period of the ACh sensitivity and Qc was about 20 min. The ACh sensitivity and Qc greatly increased at alkaline pHo and decreased at acid pHo. We suggest that the intracellular H+ ions can block the ACh-induced channel. The pHo effects may be mediated by a similar (but smaller) change in the intracellular pH (pHi). Intracellular alkalinization can improve the channel function.

Acetylcholine↗
PubMed1982

Adenosine-induced slow ionic currents in the Xenopus oocyte.

Adenosine and its 5'-phosphorylated congeners evoke specific membrane-mediated responses in excitable tissues. Available data suggest that inhibition of the target cell occurs due to hyperpolarization, and in some preparations a compound effect of ATP (excitation and inhibition) has been found. However, the ionic mechanism of the purinergic-mediated response has not been studied by standard intracellular voltage-clamping techniques. Recently, we have discovered purinergic receptors in the Xenopus oocyte, a well defined giant cell amenable to rigorous electrophysiological and biochemical studies. We report here that in these cells, adenosine-induced slow membrane responses consisted of an early depolarizing (D) transient current carried by Cl ions, followed by a steady hyperpolarizing (H) current involving K+ ions. The relative potency sequence for the D current was ATP congruent to ADP greater than AMP congruent to adenosine; this order was reversed for the H current.

Adenosine↗
PubMed1981

Divalent cations and transmitter release at low concentration of tetrodotoxin.

Transmitter release from frog motor terminals was studied in the presence of very low concentrations of tetrodotoxin (TTX, 4.10(-10)--6.10(-9) g/ml). TTX reversibly reduced the amplitude of the end-plate potential (epp), while leaving the amplitude distribution to follow Poisson's law. The effects of a number of divalent cations were studied in the presence of TTX. It was found that after the addition of TTX there was an increase in the constant of dissociation of calcium and strontium from a hypothetical membrane "release site," while the dissociation constants of magnesium and manganese remained unaltered. It is concluded that the release site is probably intracellular and that a reduced presynaptic spike amplitude, as well as magnesium and manganese ions, decrease the access of calcium and strontium to the site.

Animals↗
PubMed1980

Does rigidity in structure of muscarinic agonists and antagonists reflect drug specificity?

The present work is an attempt to elucidate: (1) whether highly rigid structural analogs of acetylcholine are still capable of activating the muscarinic receptor; (2) whether such analogs, be they agonists or antagonists, discriminate among the various ACh-mediated functions, thereby providing a tool for the study of a possible receptor heterogeneity; (3) whether structural rigidity is a significant factor in the kinetics of drug-receptor interaction. To this end, we investigated some properties of drugs in the spiro-(1,3-dioxolane-4,3')-quinuclidine system (SDQ) which embodies the muscarinic pharmacophore in a framework of utmost rigidity. Wherever possible, these properties were compared with those of a closely related but more flexible analog. Variation in effect between members of a rigid-flexible pair or among drugs of varying rigidity is considered to reflect varying affinities towards various sites of action. 2-Methyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-30) is a weak but selective muscarinic agonist. It can be viewed as a highly rigid version of 3-acetoxyquinuclidine (3-AcQ) and it can be used as a probe for detection of heterogeneity among muscarinic receptors. AF-30 is equipotent with 3-AcQ in causing tremors (mice), but has 1/17th the activity of 3-AcQ in the guinea-pig ileum, 1/30th in lowering blood pressure (cats) and 1/10th in inducing analgesia (mice). 2-Diphenylmethyl-spiro(1,3-dioxolane-4',3)-quinuclidine (AF-41) and 2.2-diphenyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-32 are potent antagonists and possess KD values in the same range as those of the more flexible congener 3-diphenylacetoxy-quinuclidine (AF-43) and atropine (0.6--2 nM) but with koff = 0.1 msec-1 (AF-41) and koff = 1 msec-1 (AF-43) (carp atrium). Thus, duration of drug action of drug action at the receptor is a function of structural rigidity in the drug molecule, termination of action being fastest with the flexible molecules. Differences in rigidity among various antagonists also find expression in an unequal distribution of potencies in various tests; thus the rigid antagonists differentiate between two central effects in mice, viz., prevention of oxotremorine-induced tremors and fall from the rotating rod by a factor of 1:20 (especially AF-41 versus AF-43), whereas the more flexible antagonists (AF-43, atropine or even 3-quinuclidinyl-benzilate) do not show such as a selectivity. The existence of heterogenous muscarinic receptors can be inferred from data presented. Both theoretical and practical implications are discussed.

Acetylcholine↗
PubMed1979

Offset rate of action of muscarinic antagonists depends on their structural flexibility.

Time course measurements of the action of muscarinic antagonists were performed in the spontaneously beating carp atrium. Several high affinity drugs, which embody the quinuclidine structure were examined. The structural flexibility of these molecules was reflected in the dissociation of the drugs from the muscarinic receptor. The dissociation of rigid drugs was very much prolonged as compared to flexible drugs of the same affinity.

Acetylcholine↗
PubMed1979

Electromechanical noise in atrial muscle cells of the carp: a possible ionic feed-back mechanism.

1. Spontaneous electrical fluctuations (+/- 0.2-0.4 mV) were recorded in 'quiescent' atrial fibres of the carp. 2. The noise decreased in acetylcholine, small hyperpolarization and EGTA. 3. The noise increased (to +/- 1-2 mV) and became more synchronous in K+-free Ringer and in ouabain. 4. Large voltage fluctuations (+/- 1-2 mV) were accompanied by a fine mechanical tremor, indicating intracellular [Ca2+] fluctuations. 5. Spectral analysis showed a clear resonant frequency at about 1 Hz, indicating that the noise cannot result from the random switching of independent ionic channels. 6. We propose that the intracellular [Ca2+] and the membrane K+-conductance are involved in a feed-back loop which can oscillate and produce the electromechanical noise. The frequency of oscillation is determined by the relatively slow diffusion of Ca2+ from the intracellular reservoir to the surface membrane.

Animals↗
PubMed1978

Acetylcholine noise in cultured chick myoballs: a voltage clamp analysis.

1. Large spherical muscle cells were grown in vitro by allowing dissociated chick myoblasts to fuse in suspension culture. 2. Myoball membranes could be adequately voltage clamped even in the face of large inward currents (ca. 100 nA) induced by ACh. 3. The single channel conductance, gamma, estimated from the ratio of the mean to the variance of ACh currents was 25-40 pmho at temperatures between 25 degrees and 37 degrees C. 4. Spectra of ACh current fluctuations declined with 1/f2. The mean channel open time (tau) estimated from the half-power frequency was 2 msec at 37 degrees C and -90 mV holding potential. At lower membrane potentials tau was decreased and on hyperpolarization tau was prolonged.

Acetylcholine↗
PubMed1978

A transition temperature for acetylcholine channel conductance in chick myoballs.

1. The temperature dependence of ACh channel conductance (gamma) and channel open time (tau) was determined by analysing ACh induced membrane current fluctuations in voltage clamped chick myoballs. 2. gamma decreased from 25-30 pmho at 37 degrees C to less than 5 phmo at 10 degrees C. An Arrhenius plot of gamma vs. temperature exhibited a clear break or 'transition temperature' at 20 degrees C. 3. tau increased from 2 msec at 37 degrees C to 16 msec at 10 degrees C. The Arrhenius plot of tau vs. temperature was linear. No transition temperature was detected. 4. Submicellar concentrations of the non-ionic detergent, Triton X-100 reversibly blocked ACh respnses. The effect was all-or-none at the molecular level. 5. These results are consistent with the possibility that the fluidity of membrane lipids in the ACh receptor micro-environment may influence the degree to which the channel can open.

Acetylcholine↗
PubMed1977

Electro-mechanical noise in atrial muscle fibres of the carp.

Steady membrane voltage fluctuations have been observed in atrial muscle fibres of the carp. These voltage fluctuations produce minute mechanical escillations, as revealed by an interference contrast microscope. The steady voltage fluctuations may be related to abnormal automaticity in the heart.

Animals↗