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Biomedical subjects

A Auerbach

Publications and source records attributed to A Auerbach.

At least 91 records · Page 5Linked to original sources
PubMed1987

Activation of the primary kinetic modes of large- and small-conductance cholinergic ion channels in Xenopus myocytes.

1. The kinetic properties of single acetylcholine (ACh)-activated ion channels in tissue-cultured Xenopus myocytes have been examined in cell-attached patches. The rates of agonist binding and channel gating were inferred from the durations of open and closed intervals from channels exposed to 40 nM-200 microM-ACh. The predominant kinetic forms of large- (gamma 60) and small-conductance (gamma 40) cholinergic channels were compared. 2. At high [ACh], bursts were defined so that they primarily reflect sojourns in activatable states. The probability that a channel is open within a burst (Po) increases between 2 and 200 microM-ACh. Po is half-maximal at approximately 5 microM for gamma 40 channels and at approximately 25 microM for gamma 60 channels. 3. Open interval durations for gamma 40 channels are distributed as the sum of two exponentials, with the slow component (tau approximately 2.8 ms) accounting for greater than 80% of the total. Open interval durations for gamma 60 channels are often distributed as a single exponential with an apparent time constant of approximately 0.8 ms. For both conductance forms of channel, open interval durations show no significant dependence on [ACh] in the range 0.04-10 microM, but decrease at higher [ACh] in a manner consistent with channel block by agonist molecules. 4. Closed interval durations within bursts (2-100 microM-ACh) for gamma 60 or gamma 40 channels are described by the sum of two or three exponentials. For both conductance forms of channel the apparent time constant of the fastest component is approximately 40 microseconds and does not change significantly with [ACh], and the time constant of the predominant, slowest component (tau slow) decreases with increasing [ACh]. 5. For gamma 40 channels, at high [ACh] tau slow saturates at approximately 0.17 ms, while no saturation is apparent for gamma 60 channel tau slow values up to 200 microM-ACh. Below 50 microM-ACh, gamma 40 tau slow values are approximately 1.5 times shorter than gamma 60 values. 6. Estimates of rate constants for agonist binding and channel gating were obtained by fitting closed interval durations in the range 2-100 microM-ACh. Gamma 60 channels have a greater than 5-fold faster opening rate, approximately 10-fold faster closing rate, and approximately 3-fold lower affinity than do gamma 40 channels. There is some indication of positive co-operativity of ACh binding to gamma 40 channels.

Acetylcholine↗
PubMed1986

Heterogeneous kinetic properties of acetylcholine receptor channels in Xenopus myocytes.

We have used the cell-attached patch-clamp technique to examine the kinetic and conductance properties of acetylcholine receptor channel currents in cultured Xenopus myocytes. At high agonist concentrations (5-100 microM) the currents occurred in bursts of openings. The probability that a channel existed in an ion-conducting conformation during a burst (Po) was adopted as an empirical measure of channel kinetic behaviour. All openings within a given burst were to the same mean current amplitude. However, different bursts could have openings with a mean conductance of either 46 pS (gamma 40) or 64 pS (gamma 60). For gamma 40 bursts there were three predominant populations which could be distinguished by their mean Po values (approximately 0.9, approximately 0.3, and less than 0.01 at 20 microM-acetylcholine). Po values increased as the acetylcholine concentration within the micropipette was increased. About 80% of bursts were from the highest Po population. gamma 60 bursts also occurred in three predominant modes. The highest Po population accounted for greater than 80% of all bursts and had a mean Po of approximately 0.6 at 20 microM-acetylcholine. For both gamma 40 and gamma 60 channels, bursts from the highest Po population had open-interval durations which were approximately 4 times longer than those from bursts from the medium Po population. Closed intervals from gamma 40, high Po bursts were approximately 4 times shorter than those from medium Po bursts. Occasional examples of switching between different kinetic modes were observed, suggesting that the Po populations may represent different activity patterns of a homogeneous channel population.

Acetylcholine↗
PubMed1985

Therapist success and its determinants.

This study examined the relatively unexplored contribution of the therapist's performance in determining outcomes of treatment. Nine therapists were studied: three performed supportive-expressive psychotherapy; three, cognitive-behavioral psychotherapy; and three, drug counseling. Profound differences were discovered in the therapists' success with the patients in their case loads. Four potential determinants of these differences were explored: patient factors; therapist factors; patient-therapist relationship factors; and therapy factors. Results showed that patient characteristics within each case load (after random assignments) were similar and disclosed no differences that would have explained the differences in success; therapist's personal qualities were correlated with outcomes but not significantly (mean r = .32); an early-in-treatment measure of the patient-therapist relationship, the Helping Alliance Questionnaire, yielded significant correlations with outcomes (mean r = .65); among the therapy techniques, "purity" provided significant correlations with outcomes (mean r = .44), both across therapists and within each therapist's case load. The three therapist-related factors were moderately associated with each other.

Adolescent↗
PubMed1984

Single-channel currents from acetylcholine receptors in embryonic chick muscle. Kinetic and conductance properties of gaps within bursts.

In tissue-cultured chick muscle, bursts of current from single nicotinic ion channels contain a variety of low-conductance gaps. One population has a lifetime of approximately 0.1 ms and an unknown conductance. A second population has a lifetime of 2-10 ms and conductance of zero. The third population has a lifetime of 0.5-1 ms and a mean conductance approximately 2% that of the main conductance state. This subconductance state has an agonist-dependent lifetime, longer for suberyldicholine than for acetylcholine, and is liganded to the same extent as the main conductance state. Subconductance gaps have a linear current-voltage behavior in the range -60 to -140 mV and appear to have the same reversal potential as the main state. The subconductance state is composed of a group of states which interconvert with correlation times longer than 300 microseconds.

Animals↗
PubMed1983

Flickering of a nicotinic ion channel to a subconductance state.

Nicotinic acetylcholine channels show bursts of activity where open channel currents are separated from each other by short closed periods called flickers. These flickers presumably represent transitions from the open state to the state preceding the first opening of a burst (doubly liganded, closed state). Using tissue cultured chick pectoral muscle, we have examined the amplitude distribution of flickers. Of those events sufficiently long to permit accurate measurement of the amplitude (approximately 25% of all flickers), approximately two-thirds had a mean current equal to 10% of the fully open channel. The remaining one-third did appear to close completely. The subconducting flicker state is not a requisite step preceding channel opening. We conclude that there are three types of flicker events: a short event (time constant approximately 0.1 ms) whose current distribution is uncertain and two longer events (time constant approximately 1 ms), one of which has a current approximately 10% of the main open state and the other of which has a current indistinguishable from zero. In contrast, the amplitude of flickers induced by the local anesthetic QX-222 is indistinguishable from zero.

Animals↗
PubMed1983

Single-channel electrophysiology: use of the patch clamp.

The patch clamp technique affords unparalleled resolution of the detailed properties of ion channel currents. Patch clamping is not difficult and has been used to record single-channel currents from many cell types. The number of artifacts associated with the method appears to be rather small. The main experimental difficulties arise from the need to process large amounts of data. With the development of inexpensive computers and mass storage devices, these problems should be alleviated. The study of membrane excitability is expanding rapidly owing to the introduction of high-resolution patch clamp techniques. The conceptual revolution that will inevitably follow is just beginning.

Animals↗
PubMed1983

Comparison of excitatory currents activated by different transmitters on crustacean muscle. I. Acetylcholine-activated channels.

The properties of acetylcholine-activated excitatory currents on the gm1 muscle of three marine decapod crustaceans, the spiny lobsters Panulirus argus and interruptus, and the crab Cancer borealis, were examined using either noise analysis, analysis of synaptic current decays, or analysis of the voltage dependence of ionophoretically activated cholinergic conductance increases. The apparent mean channel open time (tau n) obtained from noise analysis at -80 mV and 12 degrees C was approximately 13 ms; tau n was prolonged e-fold for about every 100-mV hyperpolarization in membrane potential; tau n was prolonged e-fold for every 10 degrees C decrease in temperature. Gamma, the single-channel conductance, at 12 degrees C was approximately 18 pS and was not affected by voltage; gamma was increased approximately 2.5-fold for every 10 degrees C increase in temperature. Synaptic currents decayed with a single exponential time course, and at -80 mV and 12 degrees C, the time constant of decay of synaptic currents, tau ejc, was approximately 14-15 ms and was prolonged e-fold about every 140-mV hyperpolarization; tau ejc was prolonged about e-fold for every 10 degrees C decrease in temperature. The voltage dependence of the amplitude of steady-state cholinergic currents suggests that the total conductance increase produced by cholinergic agonists is increased with hyperpolarization. Compared with glutamate channels found on similar decapod muscles (see the following article), the acetylcholine channels stay open longer, conduct ions more slowly, and are more sensitive to changes in the membrane potential.

Acetylcholine↗
PubMed1983

Comparison of excitatory currents activated by different transmitters on crustacean muscle. II. Glutamate-activated currents and comparison with acetylcholine currents present on the same muscle.

The properties of glutamate-activated excitatory currents on the gm6 muscle from the foregut of the spiny lobsters Panulirus argus and interruptus and the crab Cancer borealis were examined using either noise analysis, analysis of synaptic current decays, or slow iontophoretic currents. The properties of acetylcholine currents activated in nonjunctional regions of the gm6 muscle were also examined. At 12 degrees C and -80 mV, the predominant time constant of power spectra from glutamate-activated current noise was approximately 7 ms and the elementary conductance was approximately 34 pS. At 12 degrees C and -80 mV, the predominant time constant of acetylcholine-activated channels was approximately 11 ms with a conductance of approximately 12 pS. Focally recorded glutamatergic extracellular synaptic currents on the gm6 muscle decayed with time constants of approximately 7-8 ms at 12 degrees C and -80 mV. The decay time constant was prolonged e-fold about every 225-mV hyperpolarization in membrane potential. The Q10 of the time constant of the synaptic current decay was approximately 2.6. The voltage dependence of the steady-state conductance increase activated by iontophoretic application of glutamate has the opposite direction of the steady-state conductance activated by cholinergic agonists when compared on the gm6 muscles. The glutamate-activated conductance increase is diminished with hyperpolarization. The properties of the marine crustacean glutamate channels are discussed in relation to glutamate channels in other organisms and to the acetylcholine channels found on the gm6 muscle and the gm1 muscle of the decapod foregut (Lingle and Auerbach, 1983).

Acetylcholine↗