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J A Connor

Publications and source records attributed to J A Connor.

At least 109 records · Page 6Linked to original sources
PubMed1982

Depolarization-induced contractile activity of smooth muscle in calcium-free solution.

In calcium-free solution, strips of cat intestinal muscle developed slow, rhythmic electrical potential changes that triggered contractions. Some strips failed to develop spontaneous electrical activity in calcium-free solution but responded with contractions to depolarization by direct electrical stimulation or by treatment with barium chloride, potassium chloride, or acetylcholine. Similar results were obtained with segments of cat stomach, colon, esophagus, bladder, uterus, and vena cava, as well as with rabbit vena cava. In calcium-free saline, rat small intestinal muscle showed fast electrical activity with accompanying development of a tetanuslike contraction. After 60 min in calcium-free solution, cat small intestinal muscle retained 17.7% of its original concentration of calcium. It is concluded that in some smooth muscles, depolarization-triggered release of intracellular calcium does not require an associated influx of calcium.

Animals↗
PubMed1982

Effects of alterations in calcium levels on cat small intestinal slow waves.

Intact segments of cat intestinal muscle and strips of isolated longitudinal muscle were treated with agents that reduce intracellular calcium concentration: incubation in 0-calcium saline, treatment with calcium conductance blockers, elevated extracellular magnesium concentration, or alkalinization with NH4Cl. These treatments reduced amplitude and frequency of slow waves in intact segments but only reduced frequency in isolated longitudinal muscle. The reduction in frequency was characterized by prolongation of the hyperpolarized phase of the slow waves. Treatments that would moderately increase intracellular calcium concentration, i.e., increasing external calcium to four times normal levels or lowering pH by CO2, increased slow-wave frequency. Increased frequency was associated with reduced amplitude and shortening of the hyperpolarized phase of the slow waves. Greater than four times normal calcium levels and intense spiking reduced slow-wave frequency. Chlorotetracycline fluorescence, an indicator of intracellular calcium concentration, showed fluctuations synchronous with slow waves. It is concluded that the reactions that pace the generation of slow waves are dependent on the level of intracellular calcium.

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PubMed1980

Stoichiometry and apparent dissociation constant of the calcium-arsenazo III reaction under physiological conditions.

In vitro and in situ tests have been run to characterize the reaction of the mettalochromic indicator, arsenazo III, with calcium. Job plots as well as plots of indicator absorbance vs. [Ca2+] at different indicator concentrations show a 1:1 reaction stoichiometry. Equilibrium analysis and analysis using Adair's equation are also consistent with 1:1 complexes being formed and give estimates of 34 and 45 muM for the apparent dissociation constant. In situ tests were carried out using giant neurons from Archidoris monteryensis, a marine gastropod mollusc. Dye absorbance changes were measured during voltage clamp pulses which produced a fixed calcium influx. The dependence of absorbance change on total dye concentration is consistent with the formation of a 1:1 complex of Ca with ArIII if measurements are made during the initial period of the loading pulse, less than 300 ms, although the apparent dependency changes with longer delay in measurements from the onset of the pulse.

Animals↗
PubMed1980

Intracellular pH changes induced by calcium influx during electrical activity in molluscan neurons.

Simultaneous measurements of electrical activity and light absorbance have been made on nerve cell bodies from Archidoris monteryensis injected with indicator dyes. pH indicators, phenol red and bromocresol purple, and arsenazo III, which under normal conditions is primarily a calcium indicator have been employed. Voltage clamp pulses which induced calcium influx caused an absorbance decrease of the pH dyes indicating an internal acidification. The onset of the pH drop lagged the onset of Ca2+ influx by 200-400 ms, and pH continued to decrease for several seconds after pulse termination which shut off Ca2+ influx. Trains of action potentials also produced an internal pH decrease. Recovery of the pH change required periods greater than 10 min. The magnitude of the pH change was largely unaffected by external pH in the range 6.8-8.4. The voltage dependence of the internal p/ change was similar to the voltage dependence of calcium influx determined by arsenazo III, and removal of calcium from the bathing saline eliminated the pH signal. In neurons injected with EGTA (1-5 mM), the activity-induced internal Ca2+ changes were reduced or eliminated, but the internal pH drop was increased severalfold in magnitude. After the injection of EGTA, voltage clamp pulses produced a decrease in arsenazo III absorbance instead of the normal increase. Under these conditions the dye was responding primarily to changes in internal pH. Injection of H+ caused a rise in internal free calcium. The pH buffering capacity of the neurons was measured using three different techniques: H+ injection, depressing intrinsic pH changes with a pH buffer, and a method employing the EGTA-calcium reaction. The first two methods gave similar measurements: 4-9 meq/unit pH per liter for pleural ganglion cells and 13-26 meq/unit pH per liter for pedal ganglion cells. The EGTA method gave significantly higher values (20-60 meq/unit pH per liter) and showed no difference between pleural and pedal neurons.

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PubMed1979

Current-voltage relationships of repetitively firing neurons.

The current-voltage curves of repetitively firing neurons show non-linearities in the subthreshold region. Microsurgically isolated molluscan neuron somata were studied under voltage clamp using ramp voltage command signals. During the depolarizing 1/2 cycle a region of negative slope conductance was observed. Ion substitution experiments suggest that this results from non-inactivating or slowly inactivating Na+ and Ca2+ currents. The hyperpolarizing 1/2 cycle reveals a hysteresis effect which results at least in part from a Ca2+ activated 5+ current. Similar characteristics have been described in bursting neurons. Their occurrence in the non-bursting neurons studied here shows that they are not unique to this class of neurons and suggests that their primary contribution is to create electrical instability necessary for repetitive firing.

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PubMed1979

Calcium current in molluscan neurones: measurement under conditions which maximize its visibility.

1. Membrane currents were studied in isolated somata of molluscan neurones from Archidoris monteryensis and Anisodoris nobilis. Under voltage clamp, inward current displayed a two phase time course, and in some cases a clear reversal potential difference could be shown for the fast and slow phases. The slower phase was carried predominantly by calcium ions. 2. The apparent magnitude of the slower phase was greatly influenced by conditions which altered potassium current flow. Blocking voltage-dependent potassium conductances, either by appropriate conditioning polarizations or by tetraethyl-ammonium (TEA) ion, enhanced the magnitude, while conditions which augmented potassium current made the slow phase disappear. 3. A fraction of the membrane potassium conductance was TEA insensitive. This fraction could be blocked by procedures which prevented internal levels of calcium from increasing during the voltage clamp pulse. Three such procedures were demonstrated; replacement of external calcium by magnesium, internal buffering by EGTA, and replacement of calcium by permeant barium. 4. Internal EGTA buffering or external barium in combination with external TEA produced an extreme change in membrane current as compared with the normal time course. Membrane current, when activated by pulses up to +50 mV, was net inward and showed only fractional inactivation over time courses running to several seconds. Pulses to voltages greater than +60 mV resulted in outward current. 5. It is concluded that under normal conditions the calcium conductance has the extended time course clearly evident under the modified conditions of paragraph 4 but that the calcium flux component is easily missed. 6. In agreement with several prior studies it is also concluded that a rise in internal calcium is causally related to a rise in potassium conductance. A transmembrane flux of calcium can be uncoupled from the gK increase by appropriate buffering of internal calcium. 7. The transient potassium current, IA, which bears a resemblance to calcium-dependent potassium transients in some muscle cells did not depend upon internal calcium but instead is a voltage-activated mechanism.

Animals↗
PubMed1979

Measurement of calcium influx under voltage clamp in molluscan neurones using the metallochromic dye arsenazo III.

1. The metallochromic indicator dye, arsenazo III, was injected into somata of molluscan neurones from Archidoris monteryensis. Membrane current and dye absorbance change were simultaneously monitored under voltage clamp. 2. Absorbance measured at 660 nm increased during positive-going voltage steps large enough to activate membrane conductances. In situ idifference spectra were qualitatively similar to dye, dye-calcium difference spectra recorded in vitro. The absorbance change was abolished by either a thorough removal of external calcium or internal chelation of calcium by EGTA. It was concluded that the absorbance increase primarily reflected changing internal calcium concentration and that the calcium entered from the outside. 3. Dye absorbance increased in a nearly linear fashion during voltage clamp pulses of 100--300 msec duration. This is in qualitative agreement with electrical stuidies which demonstrated only fractional inactivation of calcium conductance during such periods. Plots of absorbance change vs. Vm peaked at +30 to +40 mV and fell off sharply until approximately +70 mV where the slope became less steep. A null or reversal of the absorbance change was generally observed aroung +110 mV. Evidence is presented that calcium influx was in some cases sufficient to cause sizeable changes in its equilibrium potential. 4. During multisecond voltage clamps the slope of the absorbance change showed a large decline. Where barium substituted for calcium as the influx species in identical clamps, the absorbance at 660 nm also increased but in a much more linear fashion. Except for a slight effect on the initial few pulses, the absorbance signal did not recover after a period of barium influx. These results suggest that part of the slope decline might result from processes related to calcium uptake and not to membrane conductance decrease. 5. Dye absorbance changes during normal and TEA action potentials were measured. Comparison of these changes with voltage clamp records indicated that calcium influx during a spike was capable of raising concentration by roughly 2 X 10(-7) M if the cell were considered to be a uniform sphere with no buffering capacity. Calcium influx during action potentials was increased dramatically by TEA, primarily as a result of a prolonged plateau phase. The existence and duration of the plateau was controlled mainly by potassium conductance systems, however. There was no evidence found for facilitation of the calcium conductance. 6. Following a moderate influx of calcium it required 20--60 sec, depending on the neurone, for the dye absorbance to return to base line (at 9 degrees C). The recovery time course showed a marked difference when examined at different wavelengths. For lambda = 660 nm there was an initial period in which the absorbance decreased rapidly, followed by a slower phase which generally carried the absorbance below the initial (prepulse) value...

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PubMed1979

On exploring the basis for slow potential oscillations in the mammalian stomach and intestine.

The basic driving unit of oscillatory electrical activity in stomach and intestine is the slow wave, a propagating depolarization of myogenic origin. The slow wave controls contractile activity in the intestine by triggering action potential bursts, while in the stomach there is both action potential and spike-free slow wave activation. This review attempts to summarize recent characterizations of the slow wave and to explore in detail the evidence, which suggests that the mechanisms which generate the electrical oscillations are quite closely coupled to metabolic processes.

Action Potentials↗
PubMed1978

A mechanism for minimizing temperature effects on repetitive firing frequency.

The magnitudes and time courses of conductance changes in molluscan neurons show marked temperature dependence. Interestingly, though, the relationship between repetitive firing frequency and stimulus current is not greatly affected by moderated temperature changes (6-8 degrees C). The transient potassium current, IA, is largely reponsible for the interspike voltage trajectory, hence, repetitive interval, in molluscan neurons. It is shown in this study that temperature dependencies of the rate constants and magnitude of the IA system are balanced in such a way that the observed temperature insensitivity of the repetitive response is predicted.

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PubMed1978

Slow repetitive activity from fast conductance changes in neurons.

Membrane properties of molluscan neural somata and crustacean axons have been studied by voltage clamp analysis. These neurons generate rhythmic discharge in response to constant current stimulation, and in certain of the molluscan neurons the discharge is spontaneous. Atransiently activated potassium conductance is prominent in both of these types of neurons. Computer simulations have been run in which this transient conductance system was incorporated into modified versions of the Hodgkin-Huxley equations. Repetitive discharge is generated that is very similar to the response of the preparation from which the simulation parameters were derived. Rhythmic, spontaneous discharge is generated on slight modification of the conductance parameters.

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PubMed1977

Neural repetitive firing: modifications of the Hodgkin-Huxley axon suggested by experimental results from crustacean axons.

The Hodgkin-Huxley equations for space-clamped squid axon (18 degrees C) have been modified to approximate voltage clamp data from repetitive-firing crustacean walking leg axons and activity in response to constant current stimulation has been computed. The m infinity and h infinity parameters of the sodium conductance system were shifted along the voltage axis in opposite directions so that their relative overlap was increased approximately 7 mV. Time constants tau m and tau h, were moved in a similar manner. Voltage-dependent parameters of delayed potassium conductance, n infinity and tau n, were shifted 4.3 mV in the positive direction and tau n was uniformly increased by a factor of 2. Leakage conductance and capacitance were unchanged. Repetitive activity of this modified circuit was qualitatively similar to that of the standard model. A fifth branch was added to the circuit representing a transient potassium conductance system present in the repetitive walking leg axons and in other repetitive neurons. This model, with various parameter choices, fired repetitively down to approximately 2 spikes/s and up to 350/s. The frequency vs. stimulus current plot could be fit well by a straight line over a decade of the low frequency range and the general appearance of the spike trains was similar to that of other repetitive neurons. Stimulus intensities were of the same order as those which produce repetitive activity in the standard Hodgkin-Huxley axon. The repetitive firing rate and first spike latency (utilization time) were found to be most strongly influenced by the inactivation time constant of the transient potassium conductance (tau b), the delayed potassium conductance (tau n), and the value of leakage conductance (gL). The model presents a mechanism by which stable low frequency discharge can be generated by millisecond-order membrane conductance changes.

Action Potentials↗
PubMed1977

Interaction between longitudinal and circular muscle in intestine of cat.

1. Slow waves recorded from isolated longitudinal muscle averaged 13 mV and had slow rate of rise (0.04 V/sec) whereas when recorded from intact segments the amplitude averaged 27 mV and the rate of rise was more rapid (0.09 V/sec), often with a notch between the initial peak and the plateau. Membrane potentials of longitudinal muscle were similar in isolated and intact preparations (- 66 mV). Resting potentials of circular muscle averaged - 67 mV.2. Small bundles of circular muscle tested in the double sucrose gap produced activity, either spontaneously or in response to stimulation, which fell into three categories: fast spikes (50-200 msec duration), slow spikes (1-5 sec duration), and small graded responses. The duration of fast spikes could be increased severalfold by the addition of TEA; the graded responses were converted to full-sized spikes by TEA.3. Treatment of circular muscle with Ca-free Krebs solution eliminated spikes, and in intact preparations reduced the amplitude and rate of rise of slow waves and eliminated the notch on slow waves.4. Current-voltage curves of longitudinal muscle show delayed rectification in the depolarizing quadrant; similar curves of circular muscle show anomalous rectification, i.e. a region where a very small current causes a large voltage change.5. Non-polarized electrotonic coupling between longitudinal and circular layers indicates low-resistance pathways. Apparent space constants of longitudinal muscle are greater when attached to circular muscle than when isolated.6. It is concluded that small slow potentials originate rhythmically in longitudinal muscle, that these spread passively to circular muscle where a regenerative amplification occurs which depends on Ca conductance and the amplified slow waves spread back to the longitudinal layer. In the intact intestine pacemaking is, therefore, separate from propagation and the circular muscle provides the bulk of depolarizing current for propagation.

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