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Biomedical subjects

G A Cottrell

Publications and source records attributed to G A Cottrell.

At least 73 records · Page 4Linked to original sources

Multiple receptor sites for a molluscan peptide (FMRFamide) and related peptides of Helix.

1. The membrane actions of some tetrapeptide amides and heptapeptide amides chemically related to the molluscan neuropeptides Phe-Met-Arg-Phe-NH2 (FMRFamide) and p-Glu-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (pQDPFLRFamide) were tested and compared on identified neurones of Helix aspersa. 2. The C-terminal sequence -Phe-NH2 was an important requirement for each of the four different actions studied: slow increase in K conductance (gK), fast increase in gK, increase in Na conductance (gNa) and decrease in gK. 3. The response of some neurones involved a combination of such actions. 4. The tetrapeptide amides FMRFamide, Phe-Leu-Arg-Phe-NH2 (FLRFamide) and Phe-Ile-Arg-Phe-NH2 (FIRFamide) were more potent than the heptapeptide amides at producing the slow increase in gK and also produced the increase in gNa, not seen at all with the heptapeptide amides. 5. The heptapeptide amides induced the fast increase in gK which was not observed with the tetrapeptide amides. 6. Evidence is presented that each of the tetrapeptide amides tested acts on the same receptor type which mediates the increase in gNa and on which the heptapeptides were inactive. 7. The results are interpreted in terms of multiple receptors each of which however appears to require the C-terminal sequence Phe-Met(or Leu)-Arg-Phe-NH2, as has been shown for some molluscan muscle preparations which react to these peptide amides (Price & Greenberg, 1980).

Action Potentials↗

Centralizing outpatient scheduling in radiology.

Centralizing outpatient scheduling in radiology has had major benefits for the hospital, say Mr. Cottrell of the experience at St. Mary's Hospital in Florida. He traces the goals, implementation and results of this new program.

Appointments and Schedules↗

Induction and suppression of seizures by cysteamine in hippocampal kindled rats.

Cysteamine has a biphasic effect in kindled rats. At a dose of 200 mg/kg (i.p.), hippocampal kindled rats all have myoclonic seizures during the first hour after injection, while naive rats seldom do. Four hours after cysteamine, the animals exhibited stage 5 seizures when stimulated. However, kindled seizures could not subsequently be elicited for up to 10 days in these animals.

Animals↗

Some neurobiological applications of the BBC Model B microcomputer and Unilab 8-bit interface.

Four computer programs written for the BBC Model B microcomputer (coupled to a Unilab 8-bit interface) are discussed. These programs enable the system to be used as (1) a transient recorder, (2) a rapid signal averager, (3) a spike-train analyser and (4) an instrument for measuring the amplitude of single channel currents. Flow-charts illustrating the operation of each program are given along with a detailed discussion of how the programs may be used in the laboratory. The discussion is illustrated using recordings taken from experiments conducted on a range of neurobiological preparations.

Animals↗

Some observations on the kindling process.

Kindling is an animal model of epilepsy in which repeated administration of a subconvulsant stimulus, electrical or chemical, produces a gradually increasing electroencephalographic and behavioral response which culminates in a behavioral seizure. The biological basis of the kindling effect remains unknown but alterations in neurotransmission figure prominently in most hypotheses. Several factors of kindling are considered as central to the phenomenon. It is most important to recognize that the development of kindling and a kindled seizure are not necessarily the same phenomenon. Kindling is essentially a permanent change in the sensitivity of the brain to a stimulus. It therefore follows that the biological basis for kindling must be a permanent change. Permanent changes in neurotransmitter levels or receptor parameters have not been conclusively demonstrated in kindling. Other possible permanent changes include changes in Ca++ activated mechanisms which alter neuronal structures such as dendritic spines. An essential component to the riddle of kindling is the absolute requirement for an inter-stimulus interval of at least 1-2 hours. This suggests that the biological process which leads to kindling occurs in this critical period. Recent experiments with cysteamine suggest that the events in this critical period can be manipulated chemically. An understanding of these events will help to clarify the biological basis of kindling.

Animals↗

Actions of GABA and ethylenediamine on CA1 pyramidal neurones of the rat hippocampus.

The effects of locally applied gamma-aminobutyric acid (GABA) and ethylenediamine were examined and compared on CA1 pyramidal neurones in slice preparations of rat hippocampus using intracellular voltage recording techniques. Each substance produced both depolarization and hyperpolarization of the dendrites; the cell body responded with hyperpolarization alone. Ion substitution experiments suggest that the depolarizing responses of the dendrites were Cl- dependent and the hyperpolarizing responses of the cell body were dependent on Cl-, which suggests that the Cl- potential (EC1) is different in the dendrites compared with the cell body. The hyperpolarizing responses of the dendrites were dependent on K+. Dendritic depolarizing responses to GABA and ethylenediamine were antagonized by bicuculline and picrotoxin whereas the dendritic hyperpolarizing response was unaffected. The hyperpolarizing responses of the cell body were more difficult to study but it appeared that they were reduced by both bicuculline and picrotoxin. The benzodiazepines flurazepam and diazepam potentiated the dendritic depolarizing responses to GABA and ethylenediamine. It also had this effect on the hyperpolarizing response of the cell body but not on the hyperpolarizing response of the dendrites.

Animals↗

Hippocampal kindling: corticosterone modulation of induced seizures.

The effect of adrenalectomy (ADX) and corticosterone replacement was studied on seizures induced by hippocampal kindling. A complex series of changes occurred in after-discharge (AD) and behavioural depression (BD) during the immediate hours after ADX, culminating at day 1 in markedly decreased AD and BD, which returned to normal over the next several days. These changes were normalized after replacement of the ADX group with low doses of corticosterone. It is concluded that the expression and maintenance of hippocampal kindled seizures is under short-term control of corticosterone.

Adrenalectomy↗

Behavioral actions of vasoactive intestinal peptide (VIP).

The effect of vasoactive intestinal peptide (VIP) was studied on fear-motivated behaviours, exploration of a novel environment and on novelty and ACTH-induced grooming. VIP was administered via a plastic cannula into the lateral ventricle. Retention of a step-through passive avoidance task was inhibited by 10 and 30 ng VIP injected 1 hour before the retention test. Extinction of pole-jumping active avoidance behaviour was facilitated by 10 and 100 ng VIP. Mild effects were observed in an open field test on exploration and grooming activity. In conclusion, VIP produces inhibitory effects on fear-motivated behaviours.

Adrenocorticotropic Hormone↗

The behavioural depression of hippocampal kindled rats is attenuated by subcutaneous and intracerebroventricular naltrexone.

Two questions were asked: Does naltrexone attenuate the behavioural depression (BD) in other models of limbic epilepsy besides amygdala kindling? Does intracerebroventricular (ICV) administration produce the same effects as subcutaneous injection, i.e., attenuation of the BD. Male wistar rats with bipolar electrodes implanted bilaterally in the dorsal hippocampus and a metal cannula in the lateral ventricle were kindled through 1 electrode and EEG recorded through the contralateral electrode. Subcutaneous (sc) and ICV naltrexone administration attenuated the BD of hippocampal kindled rats. These results further implicate the brain opioid system in the postictal phase of kindling and possibly epilepsy.

Amygdala↗

Responses of mouse spinal neurones in culture to locally applied Phe-Met-Arg-Phe-NH2.

Embryonic mouse spinal cord neurones were maintained in a primary dissociated culture with a medium free from antibiotics. Intracellular recordings were made and the effects of local application of the neuropeptide FMRFamide were tested on selected neurones. Two types of response were seen. One response was depolarizing, with an accompanying decrease in conductance. This response was probably caused by a reduction in permeability to potassium ions. The second type of response was accompanied by an increase in conductance. Such responses showed a wide variation in their reversal potentials between different neurones. A combination of permeability changes to sodium and chloride ions appeared to be responsible for these responses.

Animals↗

Multiple actions of a molluscan cardioexcitatory neuropeptide and related peptides on identified Helix neurones.

The effects of the molluscan neuropeptide Phe-Met-Arg-Phe-NH2 (FMRF amide) and related peptides (Price & Greenberg, 1977) were tested on Helix aspersa neurones. Ionophoretic application of FMRFamide depolarized and excited some neurones, but hyperpolarized and inhibited others. In some neurones the sign of the response was dependent on the membrane potential. Two responses resulted from an increase in membrane conductance, a depolarizing response mediated mainly by an increase in Na+ ion permeability, and a hyperpolarizing response mediated by an increase in K+ ion permeability. In the C1 neurone a voltage-dependent response was observed, which only occurred when the neurone was depolarized from its resting level. This response was recorded as an inward current during voltage clamp and resulted from a decrease in K current(s), possibly Ca-activated K current. More than one response may occur in a single neurone. In the C1 neurone, the K-mediated hyperpolarization occurred as well as the voltage-dependent response, while the depolarization seen in the F2 neurone was a combination of an increase in Na conductance and an increase in K conductance.

Animals↗

An inexpensive microcomputer system for analysis of single channel currents.

A description is given of a system for rapidly measuring the durations of open times and closed times of single channel currents obtained by patch clamp techniques. The apparatus required, a BBC microcomputer and a Unilab interface, is inexpensive and easy to use. An outline of the software is given and measurements of the accuracy of timings presented. Examples of analyses of single channel currents obtained from spinal neurones in cultures are also presented.

Animals↗

Serotonin, and mouse spinal neurones in cell culture.

Two different responses to serotonin have been observed. One response was a depolarization accompanied by a decrease in membrane conductance. This response was enhanced at depolarized potentials and reduced at hyperpolarized potentials; the apparent conductance change was also reduced at hyperpolarized potentials indicating some voltage sensitivity of the response. The other response was a depolarization accompanied by an increased membrane conductance. The response was enhanced at hyperpolarized potentials and reversed to a hyperpolarization at -35 to -60 mV. The total number of responsive neurones was small (5%). This might be explained by a deficiency of serotonergic input to the recorded cells, since it was shown autoradiographically that very few neurones in the cultures used exhibited a specific high-affinity uptake for the transmitter, and hence probably contained it.

Animals↗

Voltage-dependent actions of endogenous and exogenous serotonin on identified neurones.

1. Impulse activity in an identified serotonin-containing neuron (GSN) produces a slow excitatory synaptic response in another identified neuron, the A neuron. An axon process can be traced close to the follower neuron perikaryon after Lucifer Yellow injection of the GSN perikaryon. 2. The synaptic response is markedly voltage-sensitive being increased at depolarized potentials and almost abolished and not inverted at potentials in excess of about -55mV. 3. Serotonin locally applied produces a similar response. 4. The response to serotonin does not involve a change in conductance to either sodium or chloride ions, but calcium ions do appear to be important either because of their influence on potassium ion permeability or in a direct transfer of charge across the membrane. 5. Another follower neuron exhibits a complex GSN-induced synaptic response comprising a slow potential similar to that seen in the A neuron and also a fast, probably sodium dependent, potential. 6. In addition to producing a weak direct excitation of the A neuron, GSN-activation can also partly reverse accommodation and also prolong the duration of the impulse in the A neuron. 7. Exogenously applied serotonin produces a similar voltage-dependent inward current response in the GSN as seen in the A neuron. It is suggested that the receptors mediating the response on the GSNs may normally be involved in feedback regulation. 8. Cyproheptadine (reversibly), methergoline, mianserin and propranolol (all irreversibly) antagonised the response in the GSN. These agents probably all have action on the ionic mechanism underlying the serotonin response.

Animals↗

Physiological role of a slow, voltage-sensitive, synaptic response mediated by an identified serotonin-containing neurone.

In Helix, activation of an identified serotonin-containing neurone produces a slow, markedly voltage-sensitive, depolarizing synaptic potential in another identified neurone, the A neurone. Accommodation of impulse activity in the A neurone observed with repetitive applied constant-amplitude pulses is markedly reduced by activating the serotonin neurone. Activation of the serotonin neurone also prolongs the duration of the A neurone action potential.

Action Potentials↗

The structural integrity of neurons in the hippocampal slice preparation as revealed by intracellular injection of Lucifer Yellow.

Hippocampal neurons in slice preparations were injected with the fluorescent dye Lucifer Yellow CH. Pyramidal neurons in the CA1 and CA3 regions and granule cells in the area dentata were identified and their processes traced. The perikarya and dendrites of injected neurons were clearly visible. Axons could be traced in some cases for up to 500 micrometer before they passed out of the slice. In several cases dye was observed in more than one neuron after a single neuron alone was injected.

Animals↗