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Biomedical subjects

J A Connor

Publications and source records attributed to J A Connor.

119 records · Page 7Linked to original sources
PubMed1976

Relation between oxidative metabolism and slow rhythmic potentials in mammalian intestinal muscle.

Intact muscle layers separated from the small intestine of the cat were mounted in a specially designed chamber to measure electrical slow waves and NADH fluorescence simultaneously. Cooling the muscle to 17 degrees eliminated slow waves and simultaneously increased the level of fluorescence. Likewise, superfusing the muscle with a N2-bubbled glucose-free Krebs solution decreased the amplitude of slow waves and concomitantly increased fluorescence emission. In both cases, return to normal conditions reversed the effects on both slow waves and fluorescence. When signals were averaged over 30-70 slow waves, a pattern emerged with the fluorescence oscillations in phase with the electric oscillations. The NADH:NAD+ ratio reached a maximum at the most depolarized point of the slow waves and a minimum at the most polarized point between slow waves. This indicates maximum ATP utilization during the repolarization process. The correlation between redox oscillations and electrical slow wave generation is associated with cell metabolism.

Action Potentials↗
PubMed1976

A study of the effects of p-chloromercuribenzene sulfonic acid on acetylcholine-induced responses of molluscan neurons.

The effects of the organic mercurial p-chloromercuribenzene sulfonic acid (PCMBS) on the acetylcholine receptors of two types of neurons from the marine gastropod Anisodoris nobilis were studied. Cell types were distinguished by the ion-specific conductance change resulting from applied cholinergic agents: in certain cells a conductance increase to Cl resulted (Cl-neurons); in other cells a cation conductance increase resulted (D cells). Exposure of the Cl-neurons to 1 mM PCMBS at 4 degrees C had two distinct effects: 1) the sensitivity of the membrane conductance to microelectrophoretically applied carbamylcholine was blocked in a few minutes; and 2) the membrane conductance slowly increased with an inversion potential which was the same as that of the cholinergically induced response. d-Turbocurarine did not appreciably reduce this conductance increase. However, applying carbamylcholine during the exposure period to PCMBS reduced the PCMBS response. The cholinergic response of D cells was affected to a much lesser degree by PCMBS.

4-Chloromercuribenzenesulfonate↗
PubMed1975

An equivalent circuit for small atrial trabeculae of frog.

An equivalent electrical circuit has been constructed for small atrial trabecula of frog in a double sucrose gap voltage clamp apparatus. The basic strategy in constructing the circuit was to derive the distribution of membrane capacitance and extracellular resistance from the preparation's response to small voltage displacements near the resting condition, when the membrane conductance is presumably quite low. Then standard Hodgkin-Huxley channels were placed in parallel with the capacitance and the results of voltage clamp experiments were simulated. The results suggest that the membranes of the preparation cannot in fact be clamped near the control voltage nor can the ionic currents be measured directly with reasonable accuracy by axon standards. It may or may not be a realizable goal in the future to define the preparation's electrical behavior well enough to permit the ultimate quantitative description of the membrane's specific ion conductances. The result of this paper suggest that if this goal is achieved using the double sucrose gap voltage clamp, it will be by a detailed quantitative accounting for substantial irreducible errors in voltage control, rather than by experimental achievement of good voltage control.

Animals↗
PubMed1975

Neural repetitive firing: a comparative study of membrane properties of crustacean walking leg axons.

1. Repetitive activity and membrane conductance parameters of crab walking leg axons have been studied in the double sucrose gap. 2. The responses to constant current stimulus could be classified into three catagories; highly repetitive with wide firing frequency range, type I; highly repetitive with narrow frequency range, type II; and nonrepetitive or repetitive to only a limited degree, type III. The minimum firing frequency for type I axons was much greater than for other recording techniques. 3. Voltage-clamp currents in type III axons were qualitatively similar to those of squid or lobster axon. 4. The outward membrane currents of type I and II axons showed a transient phase in addition to the usual delayed current. The magnitude of this transient was a function of both the holding and test voltages. 5. The direction of the transient current reversed in potassium-rich saline. 6. The type I repetitive response in the walking leg axons appears to be generated by the same types of conductance changes that have been demonstrated in molluscan central neurons.

Animals↗
PubMed1974

A study of pace-maker activity in intestinal smooth muscle.

1. Electrical activity of longitudinal muscle from cat intestine was recorded in the double sucrose gap.2. Approximately 20% of the preparations demonstrated slow, spontaneous fluctuations of membrane voltage, slow waves. This activity, although quite uniform in a given preparation, showed considerable inter-preparation variation with respect to amplitude, frequency and wave form.3. Application of steady hyperpolarizing current decreased slow-wave frequency and increased slow-wave amplitude while depolarizing currents increased frequency and decreased amplitude.4. Some preparations with no spontaneous slow-wave activity developed slow waves when the membrane was hyperpolarized into a given range which, depending on the preparation, varied in size from 10 to 40 mV. Step or ramp depolarization of the membrane from hyperpolarized levels triggered slow waves in some preparations.5. When the membrane potential of a slow-wave generating preparation was clamped at the resting potential, spontaneous inward-directed current transients were observed.6. No changes in membrane conductance were observed during the course of a slow wave.7. The slow-wave pattern was simulated for individual preparations by applying the membrane current measured under voltage clamp to the passive membrane resistance and capacitance measured independently under current clamp.8. In addition to the defined slow-wave activity, voltage-dependent oscillations in membrane potential were sometimes observed.9. Application of 10(-5)M ouabain irreversibly blocked slow waves and produced a membrane depolarization equal to or slightly greater than the slow wave crest. Repolarization of the membrane to the resting potential, or hyperpolarization, failed to restore slow-wave activity.10. Removal of external potassium produced a reversible sequence of events almost identical to those following ouabain application.11. Replacement of 50% of the external sodium chloride with sucrose produced no changes in slow-wave activity with respect to rates of rise or fall, maximum amplitude or frequency. Sucrose replacement of all external sodium chloride eliminated slow waves after 5 min; however, activity could be restored by a slight hyperpolarization. Longer exposures to the modified bath abolished activity.12. Following a conditioning exposure to potassium-free Krebs solution, readmission of potassium at normal concentration produced a mean hyperpolarization of 20.5 mV and in spontaneous preparations an arrest of activity.13. Pump current in sodium-loaded, non-spontaneously active preparations was measured by voltage clamp and was observed to be voltage-dependent.14. The results of this study indicate that an electrogenic pump is present in longitudinal muscle of cat duodenum, and that oscillations in the level of pump current produce slow waves.

Action Potentials↗
PubMed1971

Inward and delayed outward membrane currents in isolated neural somata under voltage clamp.

1. Membrane current-voltage relationships were investigated under voltage clamp conditions in isolated neural somata of marine gastropods.2. Step depolarizations from the resting potential produce an initial inward current followed by a delayed outward current.3. Inward current appears to be carried by both sodium and calcium ions and displays time and voltage dependent properties similar to those of other excitable membranes.4. Activation and deactivation of the delayed outward current follow a more complicated time course than that of a single exponential raised to a power but can be fitted by the product of two exponential functions.5. Delayed outward current inactivation proceeds with a time constant which decreases as membrane voltage is made more positive. The steady-state levels of inactivation as a function of membrane voltage are related by an S-shaped curve similar to that for K inactivation in squid giant axon.

Animals↗
PubMed1971

Voltage clamp studies of a transient outward membrane current in gastropod neural somata.

1. Outward directed membrane currents have been studied in voltage clamp experiments on isolated neural somata of the marine gastropod Anisodoris.2. Stepping the membrane potential from a hyperpolarized level to a value in the neighbourhood of resting potential (-35 to -50 mV at 5 degrees C) results in an outward current transient, I(A), which is apparently carried by potassium ions.3. The peak amplitude of I(A) is dependent upon both the holding voltage level and the test step voltage while the time courses of development and decay are independent of, or only slightly dependent on, these parameters.4. The developing and decaying phases of I(A) are approximated by exponentials, leading to time constants for development of 10-25 msec and for decay of 220-600 msec over the aggregate of cells studied (data at 5 degrees C). Q(10) for the processes is approximately 3.5. It is concluded that the transport mechanism for I(A) is at least operationally distinct from the mechanism underlying delayed outward current, I(K).

Animals↗
PubMed1971

Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma.

1. Membrane parameters of an isolated neural cell body have been determined by voltage clamp analysis. Data are expressed as membrane ion-specific conductances, leak conductance, and capacitance.2. Three ionic currents are present: Inward, I(I); and two operationally distinct outward currents, I(K) and I(A). Both outward currents are apparently carried by potassium ions.3. Hodgkin-Huxley-like equations were solved for the discharge of two sequential action potentials in response to a constant stimulus current. The digital computer solutions are compared with action potential data recorded from the investigated cell.4. The computed and experimentally measured relationships between firing frequency and stimulus current intensity are compared and are linear over the same portion of the total frequency range.5. Cell behaviour in the latter part of the interspike interval is dominated by the conductance g(A) while g(Na) and g(K) largely determine the character of the action potential and the initial portion of the interspike interval.6. Prehyperpolarization of the membrane activates g(A) and the membrane response to depolarizing current differs markedly from the response elicited when no prehyperpolarization is imposed.

Action Potentials↗
PubMedDate not supplied

Ca2+ dynamics in neuronal growth cones: regulation and changing patterns of Ca2+ entry.

Digital ratio imaging of Fura-2 fluorescence was used to determine spatially resolved dynamics of Ca2+ changes in neuronal growth cones from the molluscs, Helisoma and Aplysia. Time resolution was approximately 1 s and spatial resolution a few mm depending upon the thickness of the cell region examined. Isolated growth cones of Helisoma were shown to recover from large Ca2+ loads over a time course of minutes, therefore demonstrating Ca2+ regulation mechanisms not dependent on the rest of the cell. Ca2+ changes monitored during action potential discharge showed sharply defined spatial gradients within the growth cones, probably arising from clustering of voltage-gated Ca-channels in the surface membrane. The regions of peak concentration change appeared to shift from central regions to the growth cone periphery as the growth cones matured. There was a marked difference in soma Ca2+ changes produced by action potentials depending on whether or not the soma had sprouted neurites. Neurite-free somata showed large Ca2+ changes, whereas in somata that had recently sprouted neurites there were almost no changes for similar electrical stimulation. Measurements on growth cones of N1E115 neuroblastoma cells showed static distributions of Ca2+ similar to those in the molluscan neurons.

Animals↗
PubMedDate not supplied

Long-term potentiation and evidence for novel synaptic association in CA1 stratum oriens of rat hippocampus.

In CA1 stratum oriens of hippocampal slices, a robust long-term potentiation (LTP) induced by tetanic stimulation (20 pulses at 100 Hz, 10 trains delivered at 0.1 Hz) was accompanied by a slowly developing potentiation in a second, untetanized pathway. N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (D-APV, 50 or 100 microM) reduced the homosynaptic LTP by 80% but failed to affect heterosynaptic LTP. The metabotropic receptor antagonist DL-2-amino-3-phosphonopropionic acid DL-AP3, 300 microM) or (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM), applied with DL-APV, further reduced homosynaptic LTP and blocked heterosynaptic LTP. The inhibitor of Ca(2+)-induced Ca2+ release dantrolene (20 microM), also applied with DL-APV, blocked both components of LTP. Importantly, when low-frequency test stimulation (0.017 Hz) to the untetanized, heterosynaptic pathway was interrupted for 30 min after homosynaptic tetanization, heterosynaptic LTP did not develop. These results demonstrate homosynaptic and heterosynaptic LTP inductions in stratum oriens of the area CA1 and suggest that the heterosynaptic LTP is induced by NMDA-independent, novel associative processes between tetanized and untetanized pathways.

Animals↗