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W W Fleming

Publications and source records attributed to W W Fleming.

At least 73 records · Page 4Linked to original sources
PubMed1978

Species differences in sodium-potassium adenosine triphosphatase activity in the smooth muscle of the guinea-pig and rat vas deferens.

The acitvities of sodium-potassium-activated adenosine triphosphatase (Na+,K+-activated ATPase) and ouabain-inhibited, sodium-potassium-activated adensoine triphosphatase (Na+,K+-ATPase) in subcellular fractions of guinea-pig and rat vasa deferentia were compared to determine whether the ineffectiveness of ouabain and reduced extracellular potassium in the rat vas deferens observed in the preceding paper occurs because of a relatively low level of Na+,K+-ATPase and/or an insensitivity to ouabain. The results indicate that the specific and total activities of Na+,K+-activated ATPase and Na+,K+-ATPase (i.e., the transport enzyme) in the individual subcellular fractions and in the tissue were higher in the vas deferens of the rat than in the guinea pig. The percentage of inhibition of Na+,K+-activated activity by ouabain (8 x 10(-5) M) varied in the subcellular fractions; it was higher in the guinea-pig (range 31--87%) than in the rat (nonsignificant effect to 40%). A greater percentage of total Na+K+- activated ATPase activity was inhibited in the vas deferens of the guinea pig (56%) than the rat (30%). Differences in the effects of lowered extracellular potassium concentration or ouabain on resting membrane potential (preceding paper) are apparently unrelated to the amount of transport enzyme in the vasa deferentia or the two species, or to its relative sensitivity to ouabain.

Animals↗
PubMed1978

Denervation-induced changes in electrophysiologic parameters of the smooth muscle of the guinea-pig and rat was deferens.

In order to further elucidate the mechanisms by which postganglionic denervation causes changes in the dose-response curves obtained in smooth muscle, microelectrodes have been used to investigate cellular changes in the denervated guinea-pig and rat vas deferens. In the guinea-pig vas deferens, chronic denervation produced a partial depolarization (mean change of 8.5 mV) without any change in threshold for the action potential. In the rat vas deferens there was no change in resting potential but the threshold membrane potential because more negative (6.5 mV). Thus, in both species, but apparently by different mechanisms, the resting and threshold membrane potentials are brought closer together by denervation. Such an effect would clearly contribute to the well documented increase in sensitivity to depolarizing agonists which is produced by chronic denervation. In both species, denervation increased the space constant of the smooth muscle, an indication of increased electrical coupling among the cells. This observation is consistent with morphologic evidence of improved coupling induced by denervation and presented previously from this laboratory. The improved coupling appears to be associated with the increased maximum response of the denervated vasa deferentia of both species. These results are discussed in references to known similarities and differences in electrophysiologic characteristics between normal guinea-pig and rat vasa deferentia.

Action Potentials↗
PubMed1978

The effects of ouabain and alterations in potassium concentration on the sensitivity to drugs and the membrane potential of the smooth muscle of the guinea-pig and rat vas deferens.

Previous work has suggested partial depolarization of the smooth muscles cells to be an important factor in the post junctional supersensitivity induced in the guinea-pig vator in the post junctional supersensitivity induced in the guinea-pig vas deferens by chronic denervation or decentralization. The present experiments were undertaken to explore, under acute in vitro conditions, the relationship between membrane potential changes and sensitivity in the vasa deferentia of guinea pigs and rats. The results indicate that sensitivity was altered whenever resting potential was changed by 7 to 10 mV. The results also indicated that considerable electrophysiologic differences exist between the smooth muscles of the guinea-pig and rat vas deferens. Notably, ouabain or lowered external potassium caused a partial depolarization of the guinea-pig, but not the rat, vas deferens. The results, especially when combined with evidence that the rat vas deferens does possess a considerable amount of (Na+-K+)-adenosine triphosphatase, which is ouabain-sensitive, indicates that under the conditions of these experiments the Na pump is electrogenic in the guinea-pig, but not the rat, vas deferens.

Animals↗
PubMed1977

A comparison of the electrical properties and morphological characteristics of the smooth muscle of the rat and guinea-pig vas deferens.

Microelectrodes were used to compare a variety of electrophysiological parameters of the rat and guinea-pig vas deferens. In comparison to the guinea pig, spontaneous junction potentials in the rat tissue were of shorter duration and occurred with greater frequency and amplitude. Action potentials induced by nerve stimulation could be observed in the smooth muscle of both species. However, in the rat tissue the majority of action potentials were generated in the impaled cell while 60% of the action potentials in the guinea-pig vas deferens were propagated. When current was intracellularly applied, spike potentials could be induced in approximately 90% of the cells of the rat vas deferens but in less than 10% of the cells of the guinea-pig vas deferens. The space constant was 1.48 mm for the guinea-pig vas deferens, but less than 0.5 mm for the rat vas deferens. Electromicroscopic examination of the homologous tissues indicates that the differences in electrical properties can be accounted for in part by differences in morphology. The incidence and intimacy of neuromuscular contacts was greater in the rat vas deferens while the incidence of nexuses between smooth muscle cells was greater in the guinea-pig tissue.

Animals↗
PubMed1977

Effects of denervation and reserpine on nexuses in the rat vas deferens.

Permanganate-fixed vasa deferentia from rats were examined for the presence of nexal-like contacts by electron microscopy. There was a significantly greater incidence of nexuses (2X) in chronically denervated tissues (5-7 days) but not in tissues from reserpine-pretreated animals (1.0 mg/kg/day for 5-7 days). The results suggest that an increase in nexal regions may not be a general feature of postjunctional supersensitivity but rather may contribute to other denervation-induced changes in contractile response.

Animals↗
PubMed1976

The effect of pretreatment with reserpine on the diastolic potential of guinea-pig atrial cells.

It has previously been suggested that the reserpine-induced nonspecific increase in sensitivity of the guinea-pig heart to the chronotropic effect od drugs occurs as a result of an alteration in the electrophysiological properties of the cell membrane. The results obtained in the present study provide support for this suggestion. The diastolic potential of atrial cells of perfused hearts obtained from guinea pigs treated with rerpine (0.1 mg/kg/day) for 7 days was significantly less than control. This treatment schedule of reserpine results in a significant increase in the sensitivity of perfoused hearts to the chronotropic effects of drugs...

Action Potentials↗
PubMed1975

Effects of various denervation techniques on the ATP of the rat vas deferens.

Postganglionic denervation of the vas deferens of the rat by surgical means or pretreatment with 6-hydroxy-dopamine results in a substantial decrease in the concentration of ATP in the tissue. The loss of ATP cannot entirely be accounted for by the loss of neuronal ATP nor by a compromised blood supply. The results suggest that the postganglionic nerve plays an important role in the regulation of the ATP of the effector cells.

Adenosine Triphosphate↗
PubMed1975

Altered resting membrane potential in the supersensitive vas deferens of the guinea pig.

Microelectrodes have been used to obtain evidence for cellular changes associated with postjunctional supersensitivity in the vas deferens. Chronic decentralization or denervation caused a partial depolarization. A study of the time course of this depolarization in decentralized vasa deferentia indicated that the phenomenon appeared and reached a plateau between the 2nd and 4th postoperative day, i. e., at the same time as postjunctional supersensitivity develops in this tissue. Junction potentials induced by transmural stimulation and measured in impaled cells were not significantly different in control and decentralized cells. The results are discussed in relation to existing theories of supersensitivity and information in the literature regarding other cellular changes, especially of calcium. It is hypothesized that postjunctional supersensitivity is due, at least in part, to a reduction in resting membrane potential associated with a decrease in calcium bound to the cell membrane.

Animals↗
PubMed1975

The correlation between spontaneous contractions and postjunctional supersensitivity of the smooth muscle of the rat vas deferens.

Chronic postganglionic denervation of the rate vas deferens produces an increase in the sensitivity of the in vitro smooth muscle to norepinephrine, methoxamine, acetylcholine, potassium and electrical stimulation. The maximal contractile response to norepinephrine and acetylcholine is increased but the maximal response to potassium or electrical stimulation is not affected. In addition, the vas deferens becomes spontaneously active after denervation. The spontaneous contractions are not prevented by tetrodotoxin, phentolamine or atropine. The appearance and magnitude of the spontaneous contractions are temporally correlated with the development of postjunctional supersensitivity. At a given time after denervation there is a significant correlation between the magnitude of the spontaneous contractions and the sensitivity to norepinephrine, i.e., the sensitivity to norepinephrine being greatest in those tissues with the largest spontaneous contractions. There is an inverse relationship between the magnitude of the spontaneous contractions and the endogenous norepinephrine concentration. Pretreatment of rats with reserpine (1. 0 mg/kg/day for 5-7 days) results in supersensitivity of the vas deferens ,o norepinephrine and acetylcholine. Those tissues obtained from reserpine-pretreated rats which are supersensitive are also spontaneously active. It is concluded that the -ppearance of spontaneous contractions in the rat vas deferens is an index of postjunctional supersensitivity.

Acetylcholine↗
PubMed1975

Electrophysiological correlations with postjunctional supersensitivity.

Several lines of evidence have been found which suggest that a partial depolarization is an important event in the development of postjunctional (nondeviation) supersensitivity in the vas deferens and atrium. In the vas deferens of the guinea pig, experiments with microelectrodes indicate that a depolarization of approximately 10 mV occurs after denervation or decentralization. The time course of the depolarization is the same as the time course of the development of supersensitivity found 7 days after denervation in the rat vas deferens. An analysis of the magnitude of junction potentials in the vas deferens supports the conclusion that changes in adrenergic receptors are not a significant factor in postjunctional supersensitivity. An analysis of membrane potential in guinea pig atria demonstrates a high correlation between the appearance of supersensitivity and a partial depolarization in that tissue alsomit is suggested that chronic interruption of the innervation to smooth or cardiac muscle leads to an alteration in the binding of calcium to the cell membrane and a consequent depolarization. The result is a resting membrane potential closer to the threshold for excitation.

Animals↗