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Biomedical subjects

C G Carlson

Publications and source records attributed to C G Carlson.

27 records · Page 2Linked to original sources
PubMed1985

The aminoglycoside antibiotic, gentamicin, fails to block increases in miniature endplate potential frequency induced by the sulfhydryl reagent, N-ethylmaleimide, in low calcium solutions.

N-ethylmaleimide (NEM) increases the frequency of miniature endplate potentials (MEPPs) at the adult rat hemidiaphragm. This sulfhydryl-alkylating agent produces comparable effects in the absence of added calcium (2 mM EGTA), suggesting that the drug releases calcium from internal stores, or promotes calcium-independent release by depolarizing the nerve terminal or interacting more directly with the release mechanism. These increases in frequency are not blocked by the aminoglycoside antibiotic, gentamicin; although the latter agent reduces quantal content and the elevations in MEPP frequency induced by high potassium solutions. The results suggest that gentamicin and NEM act at different sites at the presynaptic terminal, and that the aminoglycosides block voltage-dependent presynaptic calcium influx.

Action Potentials↗
PubMed1985

Dissociated cell culture of cholinergic neurons from nucleus basalis of Meynert and other basal forebrain nuclei.

Degeneration of cholinergic neurons from the basal forebrain nuclei is suspected to be the cause of Alzheimer disease. We have developed dissociated cultures of cholinergic neurons from these nuclei (the nucleus basalis of Meynert, the medial septal nucleus, and the diagonal band nuclei). Brain slices of the forebrains were made by a vibratome, and the basal forebrain nuclei were dissected out, dissociated, and cultured. Choline acetyltransferase immunocytochemistry and acetylcholinesterase cytochemistry revealed large cholinergic cells (average diameter, 20-25 micron) in these cultures. About 75% of large neurons (20 micron or larger in diameter) were cholinergic. Electrophysiological experiments were performed on these large neurons. The neurons usually did not show spontaneous firing, but steady depolarizations produced trains of action potentials, which adapted quickly. The neurons responded with depolarization to the application of L-glutamic acid. Substance P produced depolarization (sometimes hyperpolarization), and during the depolarization membrane resistance was increased.

Acetylcholinesterase↗
PubMed1985

Neostigmine increases the size of subunits composing the quantum of transmitter release at mouse neuromuscular junction.

Miniature end-plate potentials (m.e.p.p.s) were recorded from mouse diaphragm junctions. Noise-to-signal ratios were less than 1.3%. 1-4 X 10(3) m.e.p.p.s were recorded before and after the addition of an anticholinesterase agent. M.e.p.p. amplitude distributions showed two classes of m.e.p.p.s. The mode of the bell m.e.p.p. class was ten-twelve times that of the skew m.e.p.p. class. The amplitude distributions of the bell m.e.p.p. class showed integral peaks in the central region. The anticholinesterase agent increased the interval of the integral peaks but not the number of peaks. Experimental conditions that are necessary to demonstrate integral and stationary peaks on m.e.p.p. amplitude histograms are discussed. Data support the hypothesis that the quantum of transmitter release is composed of subunits.

Action Potentials↗
PubMed1984

The influence of 2-chloroprocaine on the subsequent analgesic potency of bupivacaine.

Isolated rat sciatic nerves were used to study the interaction between 2-chloroprocaine (2-CP) and bupivacaine (BP). Five nerves studied as controls were treated with 5 X 10(-4) M BP and the amplitude of the compound action potential (CAP) evoked by suprathreshold stimulation was measured. This concentration of BP completely blocked nerve conduction; but, following washout with normal Krebs-Ringer solution, the CAP amplitude recovered to 50% of initial values in 50 (+/- 4) min with a rate of recovery of 1.7 (+/- 0.6) %/min. In another series of experiments, five nerves were blocked first with 5 X 10(-4) M 2-CP, allowed to fully recover, and then were blocked with BP under the same conditions as the controls. Under these conditions, the half time for the recovery of CAP amplitude following BP was shortened to 25 (+/- 5) min, with a rate of recovery of 2.8 (+/- 0.3) %/min. When five nerves were exposed to a 5 X 10(-4) M solution of a 2-CP metabolite, 4-amino-2-chlorobenzoic acid, no nerve blockade was produced. When these nerves subsequently were blocked with BP, recovery to 50% of initial values occurred in 22 (+/- 5) min, with a rate of recovery of 2.0 (+/- 0.2) %/min. Although pretreatment with either 2-CP or 4-amino-2-chlorobenzoic acid significantly shortened the duration of BP-induced nerve blockade, neither drug had a significant effect on the rate of recovery once the CAP amplitude returned to measurable values.

Action Potentials↗
PubMed1983

A comparison of the effects of acute and chronic cholinesterase inactivation on spontaneous transmitter release.

The irreversible inhibitor of acetylcholinesterase (AChE), paraoxon, when given in vivo to rats in a single injection (0.23 mg/kg s.c.) raised the miniature endplate potential (MEPP) frequency to values greater than 3 times control levels in 34% of the fibers in the rat phrenic nerve-hemidiaphragm preparation. The elevated MEPP frequencies were observed in areas of extensive muscle twitching and were associated with high frequencies of giant MEPPs. Following 3 daily injections of paraoxon; the overall MEPP frequency was reduced below control levels, the frequency of giant MEPPs returned to normal, and a greater percentage of fibers showed no spontaneous activity. This depressant effect of chronic AChE inhibition on the overall MEPP frequency diminished during 1-2 weeks of daily paraoxon treatment (0.12 mg/kg s.c. paraoxon/day). After one week of recovery from 14 daily paraoxon injections (0.12 mg/kg, 1 injection/day), the original response to a single injection (0.23 mg/kg) was restored. In an attempt to determine whether paraoxon exerts its effects on spontaneous release by depolarizing the presynaptic terminal, the effect of increases in the potassium concentration on the MEPP and giant potential frequency were examined in control (saline injection) preparations, and preparations treated with 1 or 3 daily injections of paraoxon. The results suggest that paraoxon does not act by reducing the presynaptic membrane potential, but may interact more directly with the mechanism(s) responsible for regulating the release of MEPPs and giant MEPPs.

Animals↗
PubMed1982

Changes in MEPP and EPP amplitude distributions in the mouse diaphragm during synapse formation and degeneration.

Miniature end-plate potential (MEPP) and end-plate potential (EPP) amplitude histograms were examined in the mouse diaphragm during degeneration, deterioration, re-innervation and neonatal development. MEPPs and EPPs were recorded with conventional electrophysiological techniques. Control MEPP amplitude distributions from mice 21-30 days old showed two classes of MEPPs. The larger class composed 80-90% of the MEPPs and formed a bell-shaped distribution (bell-MEPPs). The smaller class (skew-MEPPs) formed a skewed distribution with a peak 1/7 to 1/15 that of bell-MEPPs. Usually, MEPP amplitude distributions did not change during the course of nerve degeneration or during deterioration in the bath. MEPP amplitude distributions from newly re-innervated fibers were composed mainly of skew-MEPPs. At later stages of re-innervation the relative numbers of skew-MEPPs decreased. Many fibers from neonatal mice (2-3 days old) also showed mainly skew-MEPPs. Rise time vs amplitude plots were constructed from neonatal and re-innervating preparations. The skew-MEPP time-to-peak measurements fell on or below the regression line calculated from the time-to-peak data of the bell-MEPPs. This indicates that the skew-MEPPs originated from the same site as the bell-MEPPs. Unitary EPPs were recorded from neonatal and re-innervating preparations by reducing the evoked response with cobalt ions (4 mM). Distributions of unitary EPPs were similar to those of bell-MEPPs. It is concluded that there are two classes of spontaneous quanta. The skew-MEPP class dominates MEPP amplitude distributions during the early stages of re-innervation and early neonatal preparations. In all stages of development the unitary evoked EPPs have the same mean amplitude and time-to-peak as the bell-MEPPs. The data suggest that the skew class is not available for evoked release.

Aging↗
PubMed1982

The effect of temperature on the amplitude distributions of miniature endplate potentials in the mouse diaphragm.

The effect of temperature (11 to 45 degrees C) on miniature endplate potential (MEPP) distributions was examined at the mouse diaphragm. MEPP distributions were composed of two populations ('skew-MEPPS' and 'bell-MEPPs') and the mode of the skew-MEPP population (subminiature endplate potential, sub-MEPP) had an amplitude equal to 1/10 to 1/15 the mean of the normally distributed bell-MEPP class. The overall MEPP frequency increased with a Q10 of 2.2 between 11 and 30 degrees C, and an Arrhenius plot indicated two temperature-sensitive reactions between 11 and 45 degrees C. Below 30 degrees C, the activation energy was 10.4 kcal/mole K and between 30 and 45 degrees C the activation energy was 38.7 kcal/mole K. The proportion of skew-MEPPs between different fibers was independent of the overall MEPP frequency and varied between 1% and 31% at temperatures of 11-34 degrees C. However, as the temperature was lowered below 24 degrees C, the decrease in frequency of skew-MEPPs was more than that of bell-MEPPs. Conversely, an increase in temperature from 24 to 34 degrees C increased the bell-MEPP frequency but either reduced or had little effect on the frequency of skew-MEPPs. Following heat challenges (T greater than 40 degrees C), MEPP distributions contained a large percentage of skew-MEPPs and the profile of the MEPP distribution became uniform. Before complete cessation of spontaneous activity with multiple heat challenges, MEPP amplitude distributions were either uniform or were composed primarily of sub-MEPPs. MEPP time courses were slower after heat challenges, and in some preparations, infections were observed on many MEPP rising phases. Amplitude histograms of these inflections yielded distributions similar to control distributions of skew-MEPPs. The presence of inflections on MEPPs following heat challenges supports the hypothesis that skew-MEPPs and bell-MEPPs are composed of subunits. These results suggest that skew- and bell-MEPPs are caused by the release of transmitter by different temperature-sensitive mechanisms.

Animals↗
PubMed1980

Effect of the Ca++ ionophore X-537A and a heat challenge on the distribution of mouse MEPP amplitude histograms.

Amplitude distributions of miniature endplate potentials (MEPPs) from the isolated mouse diaphragm neuromuscular junctions showed two classes of MEPPs at room temperature. The smaller MEPPs formed a skew distribution which composed about 15% of the MEPPs, the larger MEPPs formed a bell-shaped distribution and represented the classically studied MEPPs. In many MEPP amplitude histograms, both the skew part and bell-shaped part of the histogram showed integral peaks. The first peak is composed of s-MEPPs. The calcium ionophore (X-537A, 10(-5) M) blocked the generation of bell-shaped MEPPs leaving the s-MEPPs. There was little postsynaptic action at this low concentration. Heat challenges reversibly increased the percentage of s-MEPPs and reduced the mean of the bell distribution. Many MEPPs after either challenge had inflections on their rising phases. These observations are evidence that the larger classical MEPP is composed of subunits and the release of one subunit generates the s-MEPP.

Action Potentials↗