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K Bielefeldt

Publications and source records attributed to K Bielefeldt.

At least 19 recordsLinked to original sources
PubMed1999

Endothelin-stimulated Ca2+ mobilization by 3T3-L1 adipocytes is suppressed by tumor necrosis factor-alpha.

The cytokine tumor necrosis factor-alpha (TNFalpha) contributes to metabolic changes in disease states such as insulin resistance. However, the mechanism by which TNFalpha alters cellular function in these conditions is poorly understood. Because changes in intracellular calcium concentration plays a critical role in hormone action we investigated the effect of TNFalpha on calcium homeostasis in 3T3-L1 adipocytes. In these studies we show that TNFalpha causes a concentration- and time-dependent decrease in Na+/myo-inositol cotransporter (SMIT) mRNA levels and myo-inositol accumulation as well as a decrease in myo-inositol incorporation into phosphoinositides. These changes coincided with a decrease in endothelin-1-induced phosphatidylinositol (PI) cycle activity in 3T3-L1 adipocytes chronically exposed to TNFalpha. Endothelin-1-induced mobilization of calcium from intracellular stores was also diminished by TNFalpha. The effect of TNFalpha on endothelin-1-induced PI cycle activity and calcium mobilization was not due to a decrease in endothelin receptors. However, TNFalpha did cause a moderate decrease in phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) activity in 3T3-L1 adipocytes. Combined, a decrease in phosphoinositide production and PIP2-specific PLC activity could be responsible for altering PI cycle activity and the generation of the second messenger myo-inositol 1,4,5-trisphosphate, thereby reducing calcium mobilization. Such changes in intracellular signaling may contribute to the pathophysiology of insulin resistance associated with TNFalpha.

3T3 Cells↗
PubMed1999

Molecular diversity of voltage-sensitive calcium channels in smooth muscle cells.

Voltage-sensitive calcium channels play an important role in the excitation-contraction coupling of smooth muscle. Several subunits form the oligomeric channel complex and determine its functional properties. Therefore a differential distribution of the various channel subunits and their splice forms could contribute to the functional specialization of smooth muscle cells. To test this hypothesis, specific primers were designed to amplify messenger ribonucleic acid (mRNA) from vascular and gastrointestinal smooth muscle of the rabbit by reverse transcription and polymerase chain reaction (RT-PCR). The presence of high- and low-threshold voltage-dependent calcium channels was also examined in a smooth muscle-derived cell line (A7R5). Consistent with the physiologic data, smooth muscle contains mRNA for the pore-forming subunits of high- and low-threshold voltage-dependent calcium channels, alpha-1C and alpha-1G. Three splice variants of the alpha-1C-subunit were identified in smooth muscle. These may affect dihydropyridine binding and the interaction between the alpha-1C and the beta-subunit. In addition, three of the four cloned beta-subunits (beta-1b, beta-2, and beta-3) could be found in all smooth muscle tissues examined. These data demonstrate that various splice forms of the L-type calcium channel exist in smooth muscle tissue. Moreover, these experiments also show for the first time that smooth muscle cells contain mRNA for low-threshold voltage-sensitive calcium channels. Combinations of the pore-forming subunits with one of the three beta-subunits could account for functional differences between smooth muscle cells from distinct regions. A better understanding of the structure and function of these channels may help in our understanding of diseases affecting smooth muscle and help in the development of novel drugs targeting these molecules.

Alternative Splicing↗
PubMed1998

Differential effects of progesterone and its analogues on the contractility of the murine jejunum in vitro.

Epidemiological studies have demonstrated a higher prevalence of gastrointestinal motility disturbances in women compared with men. This may partly be due to the effects of sex hormones on smooth muscle cells. To further characterize the mechanisms by which sex hormones affect intestinal smooth muscle, we studied the effects of several structurally related progestins on intestinal contractility. Segments of the murine intestine oriented along the longitudinal axis were connected to force displacement transducers. We recorded the isometric tension generated by the murine jejunum spontaneously and after cholinergic stimulation. The baseline tension, amplitude of spontaneous contractions, and increase in tension after cholinergic stimulation were measured in the presence and absence of various steroid hormones. Progesterone dose dependently decreased the contractile activity of the murine jejunum. This effect occurred within less than 1 min and could not be inhibited by a specific blocker of the progesterone receptor, suggesting a nongenomic pathway. Experiments with several progestins demonstrated a stereoselectivity of this steroid hormone effect. This was most pronounced for dihydroprogesterone: the 5 alpha form did not affect intestinal contractility, while the stereoisomer 5 beta-dihydroprogesterone significantly inhibited smooth muscle tension. We conclude that progesterone significantly inhibits the contractility of the murine jejunum in vitro. The differential effects of various structural analogues argue against a nonspecific effect of the steroid hormones on the lipid bilayer with secondary functional alterations of membrane proteins. Rather, they suggest a specific interaction between the steroid hormone and a still unidentified protein that differs in its function and pharmacological profile from the known progesterone receptor.

20-alpha-Dihydroprogesterone↗
PubMed1998

Nitric oxide as an autocrine regulator of sodium currents in baroreceptor neurons.

Arterial baroreceptors are mechanosensitive nerve endings in the aortic arch and carotid sinus that play a critical role in acute regulation of arterial blood pressure. A previous study has shown that nitric oxide (NO) or NO-related species suppress action potential discharge of baroreceptors. In the present study, we investigated the effects of NO on Na+ currents of isolated baroreceptor neurons in culture. Exogenous NO donors inhibited both tetrodotoxin (TTX) -sensitive and -insensitive Na+ currents. The inhibition was not mediated by cGMP but by NO interaction with channel thiols. Acute inhibition of NO synthase increased the Na+ currents. NO scavengers (hemoglobin and ferrous diethyldithiocarbamate) increased Na+ currents before but not after inhibition of NO synthase. Furthermore, NO production in the neuronal cultures was detected by chemiluminescence and immunoreactivity to the neuronal isoform of NO synthase was identified in fluorescently identified baroreceptor neurons. These results indicate that NO/NO-related species function as autocrine regulators of Na+ currents in baroreceptor neurons. Modulation of Na+ channels may represent a novel response to NO.

Animals↗
PubMed1997

Calcium release from intracellular stores and excitation-contraction coupling in intestinal smooth muscle.

Calcium release from intracellular stores plays a central role in excitation-contraction coupling of striated and smooth muscle cells. Two main intracellular calcium pools have been identified in phasic smooth muscle: (1) the inositol 1,4,5-trisphosphate-sensitive and the (2) ryanodine-sensitive calcium stores. We studied the contribution of the ryanodine-sensitive calcium stores to the excitation-contraction coupling in the intestine. The intracellular calcium concentration was measured in cultured intestinal smooth muscle cells using the fluorescent probe fura-2-AM. Isometric tension generated by the murine jejunum was recorded in vitro using force displacement transducers. The cytosolic calcium level increased significantly on cholinergic stimulation. The rise persisted in the absence of extracellular calcium. Depletion of ryanodine-sensitive calcium stores with caffeine or ryanodine blunted the response to a cholinergic agonists. Similarly, the ryanodine receptor channel blocker dantrolene significantly decreased the carbachol-induced calcium increase. We subsequently tested the effects of these pharmacological tools on the spontaneous and carbachol-induced contractions of the murine jejunum. Depletion of the ryanodine-sensitive stores and calcium release channel block both significantly decreased the contractile activity of the circular and longitudinal layer of the muscularis propria. Our data confirm the importance of intracellular calcium stores in excitation-contraction coupling of intestinal smooth muscle cells. The effects of different pharmacological tools on the intracellular calcium signal and the contractile function are consistent with other observations in phasic smooth muscle. They suggest a significant contribution of calcium release from ryanodine-sensitive stores to the calcium signal that triggers contraction.

Animals↗
PubMed1997

The prostacyclin analogue carbacyclin inhibits Ca(2+)-activated K+ current in aortic baroreceptor neurones of rats.

1. Previous studies indicate that prostacyclin (PGI2) increases the activity of baroreceptor afferent fibres. The purpose of this study was to test the hypothesis that PGI2 inhibits Ca(2+)-activated K+ current (IK(Ca))in isolated baroreceptor neurones in culture. 2. Rat aortic baroreceptor neurones in the nodose ganglia were labelled in vivo by applying a fluorescent dye (DiI) to the aortic arch 1-2 weeks before dissociation of the neurones. Outward K+ currents in baroreceptor neurones evoked by depolarizing voltage steps from a holding potential of -40 mV were recorded using the whole-cell patch-clamp technique. 3. Exposure of baroreceptor neurones to the stable PGI2 analogue carbacyclin significantly inhibited the steady-state K+ current in a dose-dependent and reversible manner. The inhibition of K+ current was not caused indirectly by changes in cytosolic Ca2+ concentration. The Ca(2+)-activated K+ channel blocker charybdotoxin (ChTX, 10(-7) M) also inhibited the K+ current. In the presence of ChTX or in the absence of Ca2+, carbacyclin failed to inhibit the residual K+ current. Furthermore, in the presence of high concentrations of carbacyclin, ChTX did not cause further reduction of K+ current. 4. Carbacyclin-induced inhibition of IK(Ca) was mimicked by 8-bromo-cAMP and by activation of G-protein with GTP gamma S. The inhibitory effect of carbacyclin on IK(Ca) was abolished by GDP beta S, which blocks G-protein activation, and by a selective inhibitor of cAMP-dependent protein kinase, PKI5-24. 5. The results demonstrate that carbacyclin inhibits ChTX-sensitive IK(Ca) in isolated aortic baroreceptor neurones by a G-protein-coupled activation of cAMP-dependent protein kinase. This mechanism may contribute to the PGI2-induced increase in baroreceptor activity demonstrated previously.

Animals↗
PubMed1997

Tacrolimus (FK506) modulates calcium release and contractility of intestinal smooth muscle.

Several proteins have been identified that associate with calcium release channels and potentially regulate their function. Using tacrolimus as a pharmacological tool, we investigated whether the immunophilin FKBP12 modulates ryanodine receptor channels in intestinal smooth muscle. Results with PCR demonstrated the presence of type-3 ryanodine receptor and FKBP12 in this tissue. Tacrolimus caused an irreversible increase of the intracellular calcium concentration, which was abolished by pretreatment with caffeine. The calcium channel blocker verapamil did not affect the response to tacrolimus. Tacrolimus decreased the calcium concentration in the sarcoplasmic reticulum. Caffeine, but not inositol 1,4,5-trisphosphate or heparin, abolished this effect. Finally, tacrolimus significantly and irreversibly decreased the tension generated by intestinal muscle strips. These data support our hypothesis that the immunophilin FKBP12 modulates ryanodine receptor function in smooth muscle. Interactions between such regulatory proteins and calcium release channels may play an important role in excitation-contraction coupling and other intracellular signaling processes.

Base Sequence↗
PubMed1997

Intestinal motility during hypoxia and reoxygenation in vitro.

Ischemia-reperfusion injury leads to profound functional and structural alterations of the gastrointestinal tract. We developed an in vitro model of reperfusion injury to study the changes in intestinal motility during hypoxia followed by reoxygenation. We recorded the spontaneous motor activity of intestinal rings from the proximal mouse jejunum, using force displacement transducers. In addition to the rhythmic contractions, we studied the contractile response to transmural stimulation of intrinsic nerves. During hypoxia, the frequency of the spontaneous contractions and the resting tension decreased. While 29% of the tissues still responded to neural stimulation after 15 min of hypoxia, electrical field stimulation did not evoke any response after 60 min of hypoxia. Reoxygenation resulted in a transient increase in the baseline tension and an initial normalization of the spontaneous rhythmic contractions, which subsequently became irregular. The percentage of tissues that recovered their ability to respond to electrical field stimulation 10 min after reoxygenation decreased from 100% after 15 min of hypoxia to 47% after 60 min of hypoxia. The administration of the antioxidant glutathione prevented the functional abnormalities seen 10 min after reoxygenation. The pharmacological inhibition of Cu,Zn superoxide dismutase exacerbated the functional reoxygenation damage. Conversely, the overexpression of this radical-scavenging enzyme in transgenic mice increased the likelihood of functional recovery. Reoxygenation in a calcium-free solution also prevented prolonged functional damage of the muscle rings. We conclude that hypoxia-reoxygenation significantly alters intestinal motility. The generation of reactive oxygen species and disruptions in the calcium homeostasis play an important role in the pathogenesis of reoxygenation damage. Interventions that alter the intracellular redox state or affect the secondary changes in the intracellular calcium concentration can prevent or blunt the effects of reoxygenation injury on intestinal motility.

Animals↗
PubMed1997

Reactive oxygen species and calcium homeostasis in cultured human intestinal smooth muscle cells.

Reactive oxygen species (ROS) significantly alter cell function. We examined the effects of hydrogen peroxide (H2O2) and xanthine/xanthine oxidase (X/XO) on isolated intestinal muscle cells. We assessed cell viability with the exclusion dye trypan blue and assayed the effects of H2O2 and X/XO on the intracellular redox state with the fluorescent probe 2',7'-dichlorofluorescein. Intracellular calcium concentration was measured in cells loaded with fura 2-acetoxymethyl ester, and we recorded whole membrane currents with conventional patch-clamp methods. Cells remained viable after a 5-min exposure to H2O2 and X/XO. H2O2 and X/XO led to a significant rise of the intracellular concentration of ROS. H2O2 (270 microM to 2.7 mM) as well as X/XO (0.25-16 mU; 0.5 mM xanthine) significantly increased intracellular calcium concentrations. Depletion of intracellular calcium with ryanodine or thapsigargin did not abolish the effect of ROS on the intracellular calcium concentration. In the absence of external calcium or in the presence of the calcium channel blocker nifedipine, H2O2 and X/XO still increased the intracellular calcium level. Thus calcium influx and calcium release from internal stores contributed to this rise in cytosolic calcium. Catalase and superoxide dismutase blunted or completely abolished the changes in calcium concentration elicited by H2O2 and X/XO. Exposure to ROS resulted in a rapid decline of the membrane resistance without significant changes in voltage-sensitive ion currents. We conclude that ROS disrupt the calcium homeostasis of cells at concentrations that do not lead to immediate cell death. The resulting elevation in cytosolic free calcium will activate a variety of biochemical reactions and may thus contribute to the cytotoxicity of reactive oxygen molecules.

Acetylcholine↗
PubMed1996

Nongenomic effects of progesterone on human intestinal smooth muscle cells.

Previous experiments demonstrated that progesterone affects intestinal smooth muscle cells through genomic and nongenomic pathways. We hypothesized that the nongenomic effect was mediated by changes in membrane excitability. We studied the effects of progesterone and other steroid hormones on a human intestinal smooth muscle cell line, using the whole cell patch-clamp technique. Ionic currents were elicited through steps from -70 mV to various test potentials. Progesterone dose-dependently reduced calcium currents. The decrease in inward current was partly due to a shift in the steady-state inactivation to more hyperpolarized potentials. This effect did not involve gene transcription, since it was not blocked by the progesterone antagonist ZK-98-299. The progesterone analogue 5-beta-dihydroprogesterone also decreased calcium currents, whereas its stereoisomer, 5-alpha- dihydroprogesterone, did not affect the properties of voltage-sensitive ion channels. Similarly, estradiol and dexamethasone did not alter inward currents. We conclude that progestins exert their nongenomic effects on intestinal smooth muscle cells by decreasing calcium currents. The change in the calcium signal may contribute to the reduction in muscle contraction observed after progesterone.

Cells, Cultured↗
PubMed1994

Phosphorylation and dephosphorylation modulate a Ca(2+)-activated K+ channel in rat peptidergic nerve terminals.

1. Ca(2+)-activated K+ channels regulate the excitability of many nerve terminals. A Ca(2+)-activated K+ channel present in the membranes of rat posterior pituitary nerve terminals runs down following the formation of excised patches. This run-down process reflects enzymatic dephosphorylation. 2. Both Mg-ATP and the protein phosphatase inhibitor okadaic acid prevented run-down of channel activity in excised patches. The okadaic acid sensitivity suggests that run-down resulted from dephosphorylation by a type 1 protein phosphatase. 3. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) accelerated run-down by accelerating okadaic acid-sensitive dephosphorylation. GTP gamma S had no effect on the activity of the protein kinase in these patches. These results suggest a direct coupling between a G-protein and a protein phosphatase. 4. After run-down, channel activity could be restored by Mg-ATP; restoration depended on ATP hydrolysis, but did not require Ca2+ or a second messenger. Restoration of channel activity by ATP was blocked by staurosporine and 1-(5-isoquinolinylsulphonyl)-3-methylpiperizine, but not by more specific inhibitors of protein kinases. 5. Restoration of channel activity by phosphorylation was very sensitive to membrane potential; increasing the voltage by as little as 10 mV could dramatically enhance recovery. 6. Ca2+ and voltage acted synergistically to enhance phosphorylation; higher [Ca2+] permitted phosphorylation at more negative potentials. 7. During trains of high frequency stimulation under current clamp, action potentials were influenced by both the protein phosphatase and protein kinase, indicating that enzymatic modulation of channel gating occurs under physiological conditions. An important implication of these results is that voltage-dependent phosphorylation could play a role in use-dependent depression of secretion from nerve terminals.

Action Potentials↗
PubMed1994

Intramolecular and intermolecular enzymatic modulation of ion channels in excised membrane patches.

A calcium-activated potassium channel in posterior pituitary nerve terminals was modulated by phosphorylation and dephosphorylation. Nearly every patch of membrane containing this channel also contained both membrane bound protein phosphatase and membrane-bound protein kinase. By examining the statistical and kinetic nature of phosphorylation and dephosphorylation in excised patches, it was possible to evaluate two contrasting models for these enzymatic reactions. One of these models treated catalysis as an intermolecular process in which the enzyme and substrate are separate molecular species that diffuse and encounter one another during collisions. The second model treated catalysis as an intramolecular process in which the enzyme and substrate reside within a stable macromolecular complex. The study began with a Poisson analysis of the distribution of channel number in patches, and of the number of protein phosphatase-free and protein kinase-free patches. Subsequent kinetic analysis of dephosphorylation yielded an estimate of the mean number of protein phosphatase molecules per patch that was similar to the value obtained from Poisson analysis. Because these two estimates were independent predictions based on the intermolecular model, their agreement supported this model. Analysis of channel number in protein phosphatase-free patches and of the rarity of patches showing partial but incomplete rundown provided additional support for the intermolecular model over the intramolecular model. Furthermore, dephosphorylation exhibited monotonic kinetics with a rate well below the diffusion limit. Thus, several different lines of analysis support the intermolecular model for dephosphorylation, in which the protein phosphatase must encounter its substrate to effect catalysis. In contrast to the monotonic kinetics of dephosphorylation, the phosphorylation reaction exhibited sigmoidal kinetics, with a rate that depended on membrane potential. Voltage dependence is an unlikely property for a kinetic step involving encounters resulting from diffusion. Furthermore, the velocity of the phosphorylation reaction exceeded the diffusion limit, and this observation is inconsistent with the intermolecular model. Thus, both intermolecular and intramolecular enzymatic mechanisms operate in the modulation of the calcium-activated potassium channel of the posterior pituitary. These studies provide a functional characterization of the interactions between enzyme and substrate in intact patches of cell membrane.

Animals↗
PubMed1993

A calcium-activated potassium channel causes frequency-dependent action-potential failures in a mammalian nerve terminal.

1. The contribution of a calcium-activated potassium channel to action-potential failure was studied in nerve terminals of the rat posterior pituitary. 2. Depolarizing current injections under current clamp were faithfully followed by action potentials for stimulation frequencies of < or = 12 Hz. Further increases in frequency resulted in action-potential failure within a few hundred milliseconds. The fraction of failures increased with stimulation frequency. This decrease in excitability was concomitant with a hyperpolarization from -57.3 +/- 1.4 to -61.3 +/- 1.4 (SE) mV. 3. The decrease in excitability was dependent on calcium influx through voltage-dependent calcium channels, because action-potential failures did not occur at frequencies < or = 30 Hz in the presence of cadmium. The dihydropyridine agonist BayK 8644 increased the fraction of failed action potentials. 4. Depolarizations from -80 to 10 mV for 3 s evoked macroscopic potassium currents with a rapidly activated, transient component and a slowly developing, noninactivating component. The late outward current was dependent on calcium influx, because it was reduced by cadmium and enhanced by BayK 8644. 5. Tetraethylammonium and 4-aminopyridine effectively blocked potassium outward currents but failed to distinguish this calcium-dependent potassium channel from the other two potassium channels in this preparation. Charybdotoxin and apamin did not affect potassium currents in this preparation. 6. In excised inside-out patches, the calcium-dependent potassium channel had a slope conductance of 193 pS. The open probability changed e-fold per 14.8 mV change in membrane potential with a calcium concentration at the cytoplasmic membrane face ([Ca]i) of 100 nM. 7. The channel was highly sensitive to [Ca]i. Depolarizations to 100 mV at 10 nM [Ca]i activated the channel half-maximally. When [Ca]i was raised to 250 nM, the voltage for half-maximal activation shifted to -16 mV. Calcium also decreased the steepness of the voltage activation curve. 8. At a constant membrane potential, pressure ejection of calcium to the cytosolic face of an excised patch activated the channel with a delay of 82 ms. This slow activation in excised patches was consistent with the slow activation of the delayed component of the macroscopic current. 9. At constant calcium concentration, the time course of activation exhibited a strong voltage dependence. Most of the channels did not inactivate during depolarizations lasting < or = 300 ms. 10. The channel exhibited complex gating, with at least two distinct open and closed states.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Three potassium channels in rat posterior pituitary nerve terminals.

1. The patch clamp technique was used to investigate the K+ channels in the membranes of nerve terminals in thin slices prepared from the rat posterior pituitary. 2. Depolarization of the membrane produced a high density of K+ current. With a holding potential of -80 mV, test pulses to +50 mV activated a K+ current which was inactivated by 65% within 200 ms. Hyperpolarizing prepulses enhanced the transient K+ current, with half-maximal enhancement at -87 mV. Depolarizing prepulses reduced or eliminated the transient K+ current. 3. In cell-attached patches formed with pipettes containing 130 mM KCl, three types of K+ channel could be distinguished on the basis of single-channel properties. One channel had a conductance of 33 pS and was inactivated with a time constant of 18 ms. A second channel had a conductance of 134 pS and was inactivated with a time constant of 71 ms. A third channel had a conductance of 27 pS, was activated relatively slowly with a time constant of 65 ms, and was not inactivated during test pulses of up to one second in duration. 4. Inactivation of the whole-cell K+ current was a biphasic process with two exponential components. The fast component had a time constant of 22 ms (at +50 mV), corresponding well with the time constant of decay of average current in cell-attached patches containing only the rapidly inactivating K+ channel. The slow component of inactivation had a time constant of 104 ms (at +50 mV), which was similar to but slightly slower than the time constant of decay of the average current in cell-attached patches containing only the slowly inactivating K+ channel. Inactivation of the slow transient K+ current became more rapid with increasing depolarization. 5. The low-conductance rapidly inactivating K+ channel had a lower voltage threshold for activation than the other two K+ channels. 6. Both inactivating K+ channels were enhanced in a similar manner by prior hyperpolarization. There was no difference with regard to voltage mid-point or steepness. 7. The large-conductance slowly inactivating K+ channel was activated by Ca2+ at the inner membrane surface. The resting intracellular Ca2+ was sufficiently high to produce significant activation of this channel without depolarization-induced Ca2+ entry. 8. Removal of Ca2+ from the bathing solution produced a -10 mV shift in the voltage dependence of enhancement of both transient K+ currents by prior hyperpolarization. This could be explained as a surface charge effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Epidemiology of faecal incontinence in selected patient groups.

It is known that only a minority of patients with faecal incontinence report these symptoms to their physicians. Epidemiological estimates based on medical chart data, therefore, may contain a detection bias. To evaluate such bias in epidemiological data, we evaluated prospectively the presence of faecal incontinence in selected patient groups with a proven high incidence of such symptoms and compared it to the incidence in a group of healthy controls. If the patient acknowledged faecal incontinence in the questionnaire, the medical chart was checked to see if these symptoms had been noted during previous work-up; this was used to estimate the number of unregistered cases if the epidemiological estimate is based on medical chart data. The incidence of incontinence was significantly elevated in all patient groups as compared to the controls, but only up to 5% of patients with faecal incontinence, regardless of the underlying mechanism, had these incontinence symptoms noted in the medical charts. We conclude that for the estimation of the prevalence and incidence of faecal incontinence, data from medical charts contain a detection bias which systematically underestimates the real presence of faecal incontinence.

Adult↗
PubMed1991

Anorectal manometry and defecography in the diagnosis of fecal incontinence.

We carried out anorectal manometry and defecography prospectively in 43 consecutive patients with fecal incontinence. A subgroup of 17 patients with severe incontinence was identified radiologically by a short and incompletely closed anal canal. In these patients, the anal resting pressure was significantly lower than in the rest of the group (34.9 +/- 11.4 mm Hg versus 60.0 +/- 25.7 mm Hg, respectively; p less than 0.01). The anorectal angle did not change in 24 patients during squeezing, indicating a dysfunction of the puborectalis muscle. Manometric data did not differ between this subgroup and patients with a more acute anorectal angle during voluntary sphincter contraction. This indicates that the anal pressures recorded manometrically do not reflect the function of a muscular component that is important in the maintenance of fecal continence. We conclude that anorectal manometry and defecography are complementary diagnostic tools in the investigation of patients with fecal incontinence.

Adult↗
PubMed1991

Quantification of motor pathways to the pelvic floor in humans.

The motor innervation of the pelvic floor plays a major role in defecation disorders such as fecal incontinence. It consists of central motor pathways and peripheral nerve fibers. Transcranial magnetoelectric stimulation of the brain and magnetoelectric stimulation of the lumbosacral motor roots were performed in 10 healthy volunteers. Motor evoked potentials were recorded from the external anal sphincter. This procedure allowed differentiation between a predominantly central and a solely peripheral component of the motor innervation of the external and sphincter. To compare these recordings with well-established data, motor evoked potentials were also recorded from the anterior tibial muscle. The central motor conduction time was 20.9 +/- 2.4 ms to the external anal sphincter and 14.8 +/- 2.3 ms to the anterior tibial muscles. Central motor conduction velocities were 40.7 +/- 5.2 and 55.5 +/- 7.6 m/s, respectively. This showed that conduction in the central fibers to the external anal sphincter was significantly slower than in those to the anterior tibial muscle. We conclude 1) that magnetoelectric stimulation allows differentiation between central and peripheral portions of the motor innervation of the pelvic floor, and 2) that central motor pathways innervating the pelvic floor differ significantly in their physiological properties from those innervating limb muscles.

Adult↗