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C N Allen

Publications and source records attributed to C N Allen.

46 records · Page 3Linked to original sources
PubMed1987

Conductance properties of GABA-activated chloride currents recorded from cultured hippocampal neurons.

The conductance characteristics of gamma-aminobutyric acid-activated single channel currents from cultured hippocampal neurons were examined using patch clamp techniques. GABA-activated currents had amplitudes which were linearly correlated to the membrane potentials over a range of -80 to +70 mV and an open time and burst time of 2.2 and 4.3 ms, respectively. The conductance of the gamma-aminobutyric acid-activated channels was 19 pS. These data demonstrate that cultured hippocampal neurons have channel conductances which have characteristics different from those of adult neurons.

Animals↗
PubMed1986

Characteristics of acetylcholine-activated channels of innervated and chronically denervated skeletal muscles.

Characteristics of the ACh-activated channels before and after denervation of the frog interosseal muscle were studied using the patch clamp technique. Acetylcholine sensitivity was increased on extrajunctional portions of the muscle 7, 42, and 73 days after sectioning of the sciatic nerve. Nonjunctional regions of the innervated muscle appeared to contain one type of ACh channels having a conductance of 28 pS and a mean channel lifetime of 3.8 ms at -90 mV. The denervated muscles contained two classes of channels with conductance of 18 and 28 pS which were present as early as 7 days postdenervation and remained for 93 days. The channel open times of the innervated muscles increased with membrane hyperolarization. The open times of the channels present at 42 days postdenervation showed longer lifetimes than those of innervated muscles and were 10.8 ms and 9.6 ms at -90 mV. These channels also showed less voltage dependence than the control fibers.

Acetylcholine↗
PubMed1986

Molecular mechanisms of the potent and stereospecific nicotinic receptor agonist (+)-anatoxin-a.

Anatoxin-a (AnTX) was shown to be a highly potent and stereospecific agonist at nicotinic synapses in frog skeletal muscle and Torpedo electric organs. AnTX binds to the nicotinic-acetylcholine receptor with a higher affinity than for acetylcholine (ACh) but does not bind to sites in the receptor-gated ionic channel. (+)AnTX caused receptor desensitization, i.e., the loss of agonist-stimulated binding of histrionicotoxin to an allosteric site with time, at a rate significantly slower than that of ACh. Single channel patch clamp recordings indicated that the conductance of channels activated by (+)AnTX (28 pS) and ACh (27 pS) were similar. The (+)AnTX-activated channels contained rapid closing events, the burst times caused by the toxin were shorter than those caused by ACh but had similar voltage dependencies, and the number of short closures per burst was constant at all potentials with both agonists. The bursts of rapid openings and rapid closures (tau = 0.4 msec) appear to result from repetitive opening and closing of the (+)AnTX-bound receptor-ion channel. It is concluded that the semirigid molecule and secondary amine (+)AnTX is a more potent agonist than ACh or carbamylcholine because of a higher affinity for the receptor. At various concentrations the toxin activates the appearance of channels with the same conductances as ACh-induced channels but with a shorter channel lifetime.

Acetylcholine↗
PubMed1985

Hippocampal EEG changes in rats following cerebellar lesions.

In the rat, there is a close relation between hippocampal theta rhythm and voluntary movements. The purpose of the present study was to investigate whether motor deficits and subsequent recovery following cerebellar lesions may be accompanied by changes in hippocampal EEG. The results show that rats with severe motor dysfunctions displayed increased frequency of hippocampal theta that lasted beyond the recovery of motor deficits. Hippocampal theta that appeared along with gross automatic movements disappeared about 50 days postoperatively. The findings are discussed in terms of recovery of function and potential compensatory neural mechanisms.

Animals↗
PubMed1985

Changes in neurobiological parameters in the hippocampus after exposure to trimethyltin.

The effects of trimethyltin (TMT) on neurotransmitters, morphological changes and physiological activity of the hippocampus were studied. A single injection of TMT (8 mg/kg) decreased the high affinity uptake of glutamate (HA-Glu), which is a marker for glutamergic nerve terminals, after 7 days. The maximal reduction of HA-Glu was 42% and was obtained on postinjection day 21. Glutamate decarboxylase (GAD) and choline acetyltransferase (ChAT), markers for GABAergic and cholinergic structures, were not affected. The electrical activity of the hippocampus recorded through chronically implanted electrodes was altered by day three postinjection. The amplitude of the hippocampal electrographic record gradually decreased and the EEG ceased to be correlated with the rats' behavioral state. Fink-Heimer staining showed degenerating neurons within the subiculum, CA1, ventral CA3 and CA4 hippocampal subfields. TMT (3 mg/kg) injected once a week for three weeks decreased the HA-Glu significantly 21 days after the first injection. The HA-Glu was reduced by a maximum of 68%. The activity of ChAT was slightly increased only at day 35 postinjection while the GAD activity was not significantly reduced over a 21 day period beginning on day 14. Fink-Heimer staining showed degeneration of nerve cells within the CA1, ventral CA3 and CA4 hippocampal subfields. Both injection schedules produced degenerating neurons in the entorhinal cortex. The neurons of the dorsal CA3 region and the granule cells of the dentate gyrus were not lesioned by either TMT injection. The relationship between the behavioral, physiological and neurochemical changes induced by TMT will be discussed.

Animals↗
PubMed1984

GABAergic agents in the medial septal nucleus affect hippocampal theta rhythm and acetylcholine utilization.

Neurons of the medial septal nucleus are important in regulating the physiological activity of the hippocampus. If intraseptal injection of putative neurotransmitter substances affects the turnover rate of hippocampal acetylcholine, then concomitant changes would be expected in the electrophysiologic activity of the hippocampus. A GABA agonist, muscimol, was injected into the medial septum of rats and the effects on hippocampal electrical activity and acetylcholine utilization were studied. The intraseptally injected muscimol (100 ng) resulted in hippocampal electrographic records containing low amplitude asynchronous waves and significantly less rhythmic slow activity (RSA, 6-9 Hz), compared to control injections of saline. This effect was antagonized by prior intraseptal injection of bicuculline (3 micrograms). The hippocampal electrical activity returned to normal within 100 min. The utilization of acetylcholine was significantly reduced by intraseptal muscimol at times after administration when electrographic activity was also altered, and spontaneous behavioral movement was increased. These results suggest a physiological connection between hippocampal RSA generation and GABAergic mechanisms in the septum.

Acetylcholine↗
PubMed1984

Trimethyltin inhibits the activity of hippocampal neurons recorded in vitro.

The effects of trimethyltin (TMT) on hippocampal CA1 pyramidal cell activity was studied using an in vitro brain slice preparation. TMT (0.6 micron) reduced the orthodromic population spike and increased the threshold for population spike generation. The excitatory postsynaptic potentials (EPSP) were reduced by TMT (0.6-1.1 micron) in a dose dependent manner. The antidromically driven population spike was attenuated by TMT (0.8 micron). These results indicate that TMT alters hippocampal synaptic transmission by depression of the postsynaptic CA1 neuron. An increased perfusion time decreased the TMT dose which produced a depressive effect.

Animals↗
PubMed1984

The frog interosseal muscle fiber as a new model for patch clamp studies of chemosensitive- and voltage-sensitive ion channels: actions of acetylcholine and batrachotoxin.

The patch clamp technique was used to record the currents flowing through single ion channels in isolated frog muscle fibers. The majority of the acetylcholine (ACh)-activated channels had a conductance of 32 pS, although 20 pS channels were also occasionally observed. Lifetimes of ACh-activated channels increased with the transmembrane potential in the range from - 30 mV to - 105 mV. In these same fibers we also observed channels which were activated by low concentrations of batrachotoxin (BTX; 10 nM). These channels, presumed to be Na channels, had a conductance of 19 pS and opened at potentials at which Na channels would not normally open. A notable feature of these BTX-activated channels was that they opened and closed repeatedly. Therefore, it appears that the toxin, in addition to activating Na channels, also blocks the inactivation process. The physiological properties of these channels reveal significant differences between the ion channels of tissue-cultured and mature tissues.

Acetylcholine↗
PubMed1982

Effects of septal lesions on enzymes of acetyl-CoA metabolism in the cholinergic system of the rat hippocampus.

Electrolytic lesions made in the medial septum of the rat brain caused an 80% decrease in the activity of choline acetyltransferase and a 33% reduction in ATP-citrate lyase activity in the synaptosomal fraction from the hippocampus. Decreases in the activities of the two enzymes in the cytosol (S3) fraction were 70 and 13%, respectively. The activities of pyruvate dehydrogenase, citrate synthase, acetyl-CoA synthase, and carnitine acetyltransferase in crude hippocampal homogenates and in subcellular fractions were not affected by septal lesions. The data indicate that ATP-citrate lyase is linked to the septal-hippocampal pathway and that the enzyme is preferentially located in cholinergic nerve endings that terminate within the hippocampus.

ATP Citrate (pro-S)-Lyase↗