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1.
A. Malmgren K.-E. Andersson P.-O. Andersson M. Fovaeus C. Sjgren 《Neurourology and urodynamics》1988,7(1):27-35
Bladder strip preparations from normal female Sprague-Dawley rats as well as from rats with bladder outflow obstruction were mounted in organ baths, and isometric tension responses to electrical stimulation were recorded. Preparations of normal rat detrusor exhibited a minute spontaneous contractile activity. Addition of the calcium channel “agonist” Bay K8644 increased the basal tension and markedly enhanced spontaneous activity. In the presence of the drug the sensitivity to electrical field stimulation was enhanced; maximum amplitude increased, and the frequency producing 50% of maximum tension decreased. The calcium antagonist nifedipine had the opposite effects. In the presence of tetrodotoxin (TTX), the electrically induced responses were markedly depressed. Addition of Bay K8644 only partly restored these responses. Detrusor strips from rats with infravesical outflow obstruction exhibited marked spontaneous activity. They were less sensitive to electrical field stimulation than strips from normal bladder. Bay K8644 increased basal tension and spontaneous activity and also the maximum response to electrical stimulation. Nifedipine abolished spontaneous activity, induced a rightward shift of the frequency-response curve, and decreased the maximum amplitude. Electrically induced responses were significantly more resistant to TTX than in normal detrusor, and in the presence of TTX addition of Bay K8644 increased electrically induced response to control level. Provided that TTX completely blocks nervous transmission and that Bay K8644 and nifedipine both have a preference for voltage-operated calcium channels, these data suggest that hypertrophied bladder muscle has a nonspecific smooth muscle hypersensitivity to depolarizing stimuli. Possibly such changes can be linked to detrusor instability associated with outflow obstruction in man. 相似文献
2.
OBJECTIVES: Detrusor muscle contraction and uninhibited micturition after intravesical instillation of ice water is interpreted as a sign of upper motor neuron lesions. The basic mechanism of cooling-induced contraction (CIC) at the level of smooth muscle, however, has not been satisfactorily explained. We therefore designed model experiments with cooling of rat detrusor muscle. METHODS: We recorded isometric tension from strips of rat urinary detrusor muscle in organ baths during stepwise cooling. CIC was tested before and after addition of various standard agents interfering with known neurogenic (autonomic blockers, tetrodotoxin, capsaicin) and myogenic mechanisms of contraction (calcium channel blockers). RESULTS: Stepwise cooling (37 degrees to 5 degrees C) of detrusor muscle induced reproducible graded contractions, inversely proportional to temperature. CIC was not dependent on a neural mechanism (not blocked by tetrodotoxin or capsaicin) or the release of neurotransmitters but was linked to translocation of calcium. It was reduced by calcium channel blockers and Ca(2+)-free solution. Blockage of the Ca(2+)-adenosine triphosphatase pump, which inhibits the extrusion of calcium, also plays a significant role in the process and enhances CIC. CONCLUSIONS: Cooling of detrusor muscle preparations induces a graded myogenic contraction inversely proportional to the temperature. The mechanism is not dependent on local nervous control but is related to calcium translocation. 相似文献
3.
Electromyographic detection of purinergic activity in Guinea pig detrusor smooth muscle 总被引:4,自引:0,他引:4
PURPOSE: We recorded nerve mediated extracellular electrical activity from guinea pig detrusor smooth muscle strips using suction electrodes and determined the electrophysiological origins of this signal and its relationship to contractile activity. MATERIALS AND METHODS: Mucosa-free detrusor strips were prepared from male guinea pigs sacrificed under Home Office license, physiologically superfused, attached to a pressure transducer and electrically stimulated (0.1 millisecond pulses). Electrical signals recorded using a bipolar reversible suction electrode were processed and recorded simultaneously with changes in strip tension. The effect of superfusion with alpha, beta-methylene adenosine triphosphate (ATP), atropine, extracellular [CaCl(2)] depletion and pharmacological Ca2+ channel blockade on the electrical and mechanical signals was determined. RESULTS: A biphasic electrical signal was consistently recorded from 37 detrusor strips. The signal was sensitive to graded reduction in [CaCl(2)] of the superfusate and abolished by tetrodotoxin in 7 preparations. The signal was also abolished in 12 preparations by alpha, beta-methylene ATP in association with an attenuated contraction but not significantly reduced in amplitude (p = 0.77) despite a significant reduction in tension with atropine (mean plus or minus SD 74% +/- 14% of control, p <0.001). The signal was attenuated to a mean maximum of 9% +/- 3% of control by pharmacological Ca2+ channel blockade and the remaining signal was abolished by alpha, beta-methylene ATP. CONCLUSIONS: The extracellular electrical signal recorded from guinea pig detrusor strips using suction electrodes originates from a purinergic mechanism. Although an atropine sensitive component may be present, the signal does not depend on cholinergic neuromuscular transmission and would not be expected to be generated by normal human detrusor. Provided that the electrophysiological basis of purinergic neurotransmission in guinea pig and human bladders is similar suction electrodes may be a valuable tool with which to evaluate in vitro and clinically by electromyography the pathological purinergic neuromuscular transmission that can be expressed in addition to normal cholinergic mechanisms in detrusor from dysfunctional human bladders. 相似文献
4.
PURPOSE: Detrusor instability is a common problem in the elderly, which is usually treated with anti-cholinergic medication. This study investigates the effect of erythromycin on rat detrusor muscle contractile response to characterise its potential as an alternative inhibitor of bladder muscle contraction. MATERIALS AND METHODS: Strips of rat detrusor muscle were suspended in a perfusion organ bath. The contractile response to direct muscle stimulation, electrical field stimulation (EFS, 0.5-60 Hz), carbachol (10(-5) M), and potassium (10-80 x 10(-3) M) were determined before and after the addition of erythromycin (10(-4)-10(-3) M). The contractile response to carbachol (10(-5) M) in the presence of nifedipine (10(-8) or 10(-6) M) or in calcium-free Kreb's solution was also determined in the absence and presence of erythromycin. RESULTS: Erythromycin 5 x 10(-4) M inhibited the maximum contractile response to EFS, carbachol, and potassium by 38% (P < 0.01), 62% (P < 0.001), and 17% (P < 0.05), respectively, but did not significantly reduce the response to direct muscle stimulation. The atropine-resistant component of EFS-evoked contraction was inhibited by 19.5% (P < 0.01) in the presence of erythromycin. In calcium-free Krebs solution, the maximum contractile response to carbachol was reduced by 42% of control (P < 0.0001) and nifedipine 10(-8) M had no additional effect. When erythromycin 5 x 10(-4) M was added together with nifedipine 10(-8) M, the response to carbachol was inhibited by a further 25% (P < 0.005). CONCLUSIONS: Erythromycin inhibits rat detrusor muscle contraction through the inhibition of calcium influx and the modulation of intracellular calcium movement. 相似文献
5.
An in vitro pharmacological study of the human trigone--a site of non-adrenergic, non-cholinergic neurotransmission 总被引:4,自引:0,他引:4
Muscle strips from the human detrusor and trigone were studied in vitro. The detrusor muscle contracted strongly to both cholinergic receptor stimulation with carbachol and to electrical field stimulation. There was no evidence of atropine resistance in the detrusor strips. The superficial trigone responded maximally to alpha-adrenergic receptor stimulation but also produced a significant cholinergic response. Intramural nerve stimulation in the presence of both atropine and phentolamine produced a residual non-adrenergic, non-cholinergic (NANC) response of 40% of its maximum at 5 Hz. Electrical stimulation, particularly at the lower frequencies of stimulation, produced relaxation responses in 40% of the superficial trigonal muscle strips. These relaxations were not blocked by atropine, phentolamine or propranolol, but were abolished by tetrodotoxin. The possible role of the cholinergic "input" to the superficial trigone and the importance of the NANC excitatory and inhibitory innervation in preventing vesico-ureteric reflux and and in aiding bladder neck opening is discussed. 相似文献
6.
Isolated submucosal (lamina propria) preparations from the female rabbit urethra exhibited both contractant and relaxant properties. The nerve-mediated contraction to electrical field stimulation was adrenergic in nature, and both this response and the contraction induced by exogenous application of noradrenaline were blocked to a greater extent by alpha 2 than by alpha 1-adrenoceptor blocking agents. Vasoactive intestinal polypeptide was found to be a potent inhibitor of the noradrenaline-mediated contraction. Neuropeptide Y induced contraction of the preparation, but also inhibited the nerve-mediated contractant response. In noradrenaline-contracted preparations, electrical field stimulation induced a non-adrenergic, non-cholinergic relaxation. The maximum relaxant response was significantly greater when the preparations were contracted by clonidine than by noradrenaline. Abundant smooth muscle cells with no obvious connection to vessel walls were found in the submucosa, but to what extent the contractant and relaxant responses can be ascribed to vascular or non-vascular smooth muscle is not settled. The results indicate a non-uniform distribution of the peripheral nervous control within the wall of the female rabbit urethra. The demonstrated contractant and relaxant properties of the submucosal tissue might be of importance for urethral function. 相似文献
7.
OBJECTIVE: To elucidate the role of the membrane potential in human detrusor smooth muscle contraction, by simultaneously recording mechanical and intracellular electrical activity in muscle strips. Materials and methods The agonists acetylcholine and carbachol were applied to induce a contraction on muscarinic receptor stimulation; to block the response, atropine was added to the bath. The Ca2+ necessary for activating the contractile machinery can be recruited via two pathways: release from intracellular stores or influx from the extracellular matrix. High potassium was applied to induce Ca2+ influx through voltage-sensitive Ca2+ channels. RESULTS: There were significant changes in the force when agonist, antagonist and high potassium was administered. However, there were significant changes in membrane potential only when KCl was applied to the bath and not with muscarinic agonist or antagonist application. Activity in the form of spike potentials did not change significantly on applying any of the test substances. CONCLUSION: The present results indicate that the Ca2+ mobilized on M3 receptor stimulation originates primarily from intracellular stores, with no systematic changes in membrane potential. Atropine only caused a relaxation in muscle previously contracted by M3-receptor agonist stimulation; it had no effect on relaxed muscle strips. 相似文献
8.
Effect of bumetanide on toluene diisocyanate induced contractions in guinea pig airways. 总被引:1,自引:0,他引:1
C E Mapp A Boniotti A Papi C A Maggi A Di Stefano M Saetta A Ciaccia L M Fabbri 《Thorax》1993,48(1):63-67
BACKGROUND: The loop diuretic frusemide has been shown to inhibit the bronchoconstrictor response to exercise, inhaled allergen, distilled water, adenosine, and sodium metabisulphite. Toluene diisocyanate contracts smooth muscle by activating capsaicin sensitive nerves and causes asthma that shares many features with allergen induced asthma. METHODS: The study was designed to assess the effect of two loop diuretics, bumetanide (10 and 100 microM) and frusemide (100 microM), on smooth muscle contraction induced by toluene diisocyanate (0.03-1000 microM) in guinea pig airways with and, in the case of bumetanide, without epithelium. The effect of bumetanide on the response to acetylcholine, neurokinin A, and electrical field stimulation in guinea pig bronchial smooth muscle rings was also examined. RESULTS: Bumetanide (10 and 100 microM) had no effect on toluene diisocyanate induced contraction whether airway epithelium was present or not. Frusemide (100 microM) caused no significant inhibition of toluene diisocyanate induced contraction (mean reduction on the entire curve 25%). Bumetanide inhibited non-adrenergic, non-cholinergic contraction induced by electrical field stimulation of bronchi pretreated with atropine (1 microM) and indomethacin (5 microM) and this inhibition was inversely related to the frequency of stimulation, suggesting that bumetanide may be inhibiting transmitter release at the prejunctional level. Bumetanide and frusemide did not inhibit the responses to exogenous acetylcholine (0.1 microM) or neurokinin A (1 nM). CONCLUSIONS: Bumetanide and frusemide in doses that are known to inhibit non-adrenergic, non-cholinergic contraction due to electrical field stimulation failed to inhibit the response to toluene diisocyanate in guinea pig airways. 相似文献
9.
Protein kinase c regulates purinergic component of neurogenic contractions in mouse bladder 总被引:2,自引:0,他引:2
PURPOSE: We evaluate the role of protein kinase C in excitatory purinergic neurotransmission in the mouse bladder. MATERIALS AND METHODS: In isolated mouse detrusor strips contractile responses to electrical field stimulation were mostly mediated by neural released acetylcholine and adenosine triphosphate (ATP). The changes in neurotransmission were measured indirectly by recording the contraction of detrusor strips in response to repetitive electrical field stimulation by trains of electrical pulses at 8 Hz. 1 second in duration. RESULTS: A protein kinase C activator, 1 to 2.5 nM. (beta-phorbol-12,13-dibutyrate (beta-PDBu), but not the inactive form alpha-phorbol-12,13-dibutyrate, significantly enhanced neurogenic detrusor contractions. The purinergic component of the evoked detrusor contractions in the presence of atropine was specifically sensitive to this enhancing effect by beta-PDBu but the cholinergic component in the alpha,beta-methylene ATP treated detrusors remained unaffected. This enhancing effect of beta-PDBu was dependent on the extracellular calcium (Ca2+) concentration. A P and/or Q type Ca2+ channel blocker, 0.1 and 0.3 microM. omega-conotoxin-MVIIC, and protein kinase C inhibitors, 0.3 and 1 microM. staurosporine and 0.3 and 1 microM. bisindolylmaleimide I but not 0.1 and 0.3 microM. omega-conotoxin-GVIA, an N type Ca2+ channel blocker, abolished the effect of beta-PDBu. Moreover, beta-PDBu did not affect the muscle responses induced by the exogenous agonists carbachol or alpha,beta-methylene ATP and potassium chloride. CONCLUSIONS: These results suggest that the activation of Ca2+ channel, especially the P and/or Q type, may be involved in the enhancing effect of protein kinase C activator beta-PDBu on muscle contractions elicited by excitatory purinergic neurotransmission in the mouse detrusor strips. 相似文献
10.
Neuromuscular transmission in the corpus-fundus of the urinary bladder. An in vitro study in the cat 总被引:1,自引:0,他引:1
A Nerg?rdh 《Scandinavian journal of urology and nephrology》1981,15(2):103-108
In muscle strips from the corpus-fundus of the cat bladder the intramural nervous system was activated by field stimulation. The resulting muscle contraction could not be inhibited by atropine, phentolamine or quinidine. These drugs enhanced the response. Tetrodotoxin, methysergide, cyproheptadine and indomethacin blocked the field-stimulation response in a dose dependent manner. The interpretation of these results with references to transmission at the neuromuscular junction of the bladder is discussed. 相似文献
11.
The effect of atropine on the isometric contractile response of isolated human detrusor muscle strips to electrical field stimulation has been studied. A 94.1% reduction in the response in the presence of tetrodotoxin demonstrated the neuronal nature of the stimulus. Atropine caused a 92.7% inhibition of the response. It was concluded that the nerve-mediated stimulus in human detrusor is cholinergic in nature and that "atropine resistance" does not occur in man. 相似文献
12.
Pathophysiology of idiopathic detrusor instability and detrusor hyper-reflexia. An in vitro study of human detrusor muscle 总被引:3,自引:0,他引:3
Muscle strips from urodynamically normal bladders and from bladders exhibiting idiopathic detrusor instability or detrusor hyper-reflexia were compared under isometric conditions in an organ bath. Spontaneous contractions developed more often in unstable and hyper-reflexic muscle and were of greater amplitude, frequency and basal tension. Electrical field stimulation caused a frequency-dependent contraction which was largely abolished by both tetrodotoxin (TTX) and atropine in all three muscle types. Comparison of their frequency response curves demonstrated a significantly greater sensitivity than that of unstable and hyper-reflexic muscle to low stimulation frequencies. Acetylcholine caused a dose-related contractile response in all muscle types. There were no significant differences between the dose response curves of unstable and hyper-reflexic muscle, and those of normal muscle. The results suggest that the pathophysiology of the involuntary detrusor contraction is common to both idiopathic detrusor instability and detrusor hyper-reflexia and that this is related to a disorder of an intrinsic neuromodulatory mechanism within the detrusor muscle. 相似文献
13.
Field stimulation of rabbit corporus cavernosum tissue strips can result in relaxation, contraction, or a biphasic response depending on the frequency and the power utilized. In this study we characterized the autonomic components of this response by exposing corporal tissue strips to a variety of autonomic agonists and antagonists including phentolamine, isoproterenol, methoxamine, propranolol, bethanechol, atropine, and ATP. Low frequency electrical field stimulation produced a bi-phasic response characterized by an initial relaxation followed by a contraction. High frequencies (≥ 32 Hz) produced contraction only. All responses were abolished by tetrodotoxin, indicating that both the contractile and relaxant responses to field stimulation are mediated by complex neural mechanisms. The initial relaxation response involves a combination of mediators which include musca-rinic cholinergic stimulation, purinergic, beta-adrenergic, and non-adrenergic, non-cholinergic (NANC) stimulation. The non-cholinergic contribution to corporal smooth muscle relaxation appeared to be approximately equal in significance to the cholinergically mediated relaxation. Beta adrenergic stimulation mediated a direct relaxation of the corporal smooth muscle. The contractile portion of the bi-phasic response was mediated by alpha-adrenergic stimulation. Additionally we have noted a rebound contraction following termination of field stimulation at all frequencies that is not affected by adrenergic or cholinergic blockade and may reflect the field-stimulated release of an endogenous smooth muscle contractile factor. 相似文献
14.
Hudman D Elliott RA Whitaker P Terry TR Sandhu DP Norman RI 《The Journal of urology》2001,166(5):1969-1973
PURPOSE: We investigated the inhibition of the contractile responses of human continent and unstable detrusor muscle by the beta2 agonist clenbuterol as well as the inhibition of electrical field stimulation evoked contractile responses of isolated rat bladder muscle strips by orally administered clenbuterol. MATERIALS AND METHODS: The contractile responses of human continent and unstable detrusor muscle strips to electrical field stimulation (0.05 milliseconds, 0.5 to 80 Hz.) were measured before and after adding 10(-9) to 10(-4) M. clenbuterol in vitro. In addition, 6 rats per group were dosed orally with 2 microg x kg(-1) clenbuterol daily acutely (1 dose) or chronically (1 dose daily for 8 days), or with distilled water to serve as controls. The contractile response to electrical field stimulation of strips of isolated detrusor muscle was then measured. Serum clenbuterol levels were analyzed in duplicate by enzyme-linked immunosorbent assay and high performance liquid chromatography. RESULTS: In vitro clenbuterol significantly inhibited the electrical field stimulation evoked contractile responses of detrusor muscle strips from unstable but not continent human bladders. A significant inhibitory effect of clenbuterol on the electrical field stimulation evoked contractile response of rat detrusor muscle was observed after chronic but not acute oral dosing (p <0.01). Serum clenbuterol levels measured by enzyme-linked immunosorbent assay and high performance liquid chromatography were not significantly different. CONCLUSIONS: Clenbuterol or related beta2-adrenoceptor agonists may represent a useful therapeutic strategy for detrusor muscle overactivity. 相似文献
15.
HANS J. PIECHOTA STEFAN E. DAHMS LORA S. NUNES RAJVIR DAHIYA TOM F. LUE EMIL A. TANAGHO 《The Journal of urology》1998,159(5):1717-1724
Purpose
To assess the response of rat urinary bladder regenerated by the homologous bladder acellular matrix graft (BAMG) to in vitro electrical and pharmacologic stimuli.Materials and Methods
In Sprague-Dawley rats, partial cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After 4 months, organ bath studies of tissue strips in 10 were used to compare the contractility of the BAMG regenerates and the corresponding host detrusor smooth muscle.Results
The BAMG regenerates exhibited contractile activity to electrical field stimulation and a qualitatively identical pattern of response to muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG regenerates to carbachol stimulation amounted to close to 80% of the host bladder response. With electrical field stimulation, they equaled 44% and 62% of the host bladder response after 2.5 and 4 months, respectively. Histological and immunohistochemical studies confirmed the presence of receptors for neurotransmitters that these functional in vitro studies implied.Conclusions
The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle. 相似文献16.
Does the distal rectal muscle in anorectal malformations have the functional properties of a sphincter? 总被引:1,自引:0,他引:1
Smooth muscle strips from the distal rectum of 11 patients who underwent surgery for imperforate anus and cloacal malformations, were studied in vitro to assess the motility response to electrical field stimulations (EFS) and to pharmacological stimulation with adrenergic and cholinergic agonists. EFS induced a nonadrenergic, noncholinergic inhibition in most strips. Acetylcholine caused either a modest contraction, no response, or a relaxation. Following atropine administration, acetylcholine caused a nonadrenergic and tetrodotoxin-resistant relaxation. The alpha-adrenergic agonist phenylephrine induced contractions in all strips. The response was abolished by alpha-adrenoceptor blockade with phentolamine, but was resistant to atropine and tetrodotoxin. beta-Adrenergic stimulation caused a relaxation that was abolished by propranolol. Function of the distal rectal smooth muscle, resected during correction of anorectal malformations, shows similarities to the function reported previously on normal anal smooth muscle evaluated in vitro. 相似文献
17.
Effects of cromakalim (BRL 34915) and pinacidil on normal and hypertrophied rat detrusor in vitro 总被引:1,自引:0,他引:1
A Malmgren K E Andersson P O Andersson M Fovaeus C Sj?gren 《The Journal of urology》1990,143(4):828-834
Normal and hypertrophied rat detrusor were investigated in vitro with regard to effects of the K(+)-channel openers pinacidil and cromakalim. Both drugs abolished spontaneous contractile activity and induced a relaxation of normal and hypertrophied detrusor preparations. In both types of preparation, contractions elicited by K+, carbachol or electrical field stimulation were depressed in the presence of the K(+)-channel openers. Responses induced by K+ or electrical stimulation were more reduced in the hypertrophied than in the normal detrusor. Both K(+)-channel openers increased the efflux of 86Rb+ in a concentration-dependent way and this increase was similar in normal and hypertrophied detrusor. If applicable to man, this data suggest that K(+)-channel openers may be effective in the treatment of bladder instability secondary to outflow obstruction. 相似文献
18.
Effects of vasoactive intestinal polypeptide on isolated urethral and urinary bladder smooth muscle from rabbit and man 总被引:3,自引:0,他引:3
Vasoactive intestinal polypeptide concentration-dependently inhibited the contractant responses of isolated preparations of the female rabbit bladder and urethra induced by electrical field stimulation and exogenous application of acetylcholine (bladder) and noradrenaline (urethra). The inhibition of alpha-adrenoceptor and muscarinic cholinoceptor-mediated activity in the urethra and bladder amounted to 50 to 90 per cent of induced contractions. The nonadrenergic noncholinergic contraction induced by electrical field stimulation in the urethra was reduced slightly, whereas corresponding response in the bladder was more sensitive. The maximum inhibition of both the electrically induced responses and contractions induced by exogenous noradrenaline and acetylcholine was of comparable size in the urethra and the bladder. The effects of vasoactive intestinal polypeptide seemed to be exerted postjunctionally since no significant influence of the peptide was seen on the release of 3H-noradrenaline from adrenergic nerve endings in the urethra. The effects of vasoactive intestinal polypeptide in human urethral and bladder preparations were less consistent. The noradrenaline-induced contraction in urethral preparations was inhibited by 29 +/- 9 per cent (no. = 22). The effects on electrically induced contractions in the urethra, and on responses to acetylcholine and electrical field stimulation in the bladder, were small and inconsistent. It is concluded that vasoactive intestinal polypeptide may be of importance for regulation of lower urinary tract smooth muscle activity in the rabbit. It cannot be excluded that the peptide has a modulatory role in neurotransmission in human urethral muscle. However, the present results do not support the view of vasoactive intestinal polypeptide as an inhibitor of contraction in human detrusor. 相似文献
19.
OBJECTIVE: To explore the role of Ni(2+)-sensitive T-type Ca(2+) channels in the generation of spontaneous excitation of detrusor smooth muscles. MATERIALS AND METHODS: In isolated detrusor smooth muscle bundles of the guinea-pig bladder, changes in the membrane potential and muscle tension were measured using intracellular microelectrodes and isometric tension recording. Changes in the intracellular Ca(2+) concentration were recorded from bundles loaded with the fluorescent dye fura-PE3. RESULTS: Detrusor smooth muscles had two types of spontaneous electrical activity, i.e. individual and bursting action potentials. Ni(2+) (30 microM), a blocker for T-type Ca(2+) channels, reduced the frequency of individual action potentials without changing their amplitude. Higher concentrations of Ni(2+) (100-300 microM) converted individual action potentials into the bursts, as did apamin (0.1 microM), a blocker of small-conductance Ca(2+)-activated K(+) channels (SK). They also increased the amplitudes of spontaneous Ca(2+) transients and corresponding contractions whilst reducing their frequencies. In preparations which generated bursting action potentials, nifedipine (1 microm) converted action potentials into spontaneous transient depolarizations (STDs), and subsequent applications of Ni(2+) (100 microm) abolished STDs. Gadolinium (100 microM) and SKF96365 (10 microM), blockers for nonselective cation channels, and niflumic acid (100 microm), a blocker for Ca(2+)-activated Cl- channels, had no effect on either the amplitude or frequency of spontaneous action potentials. CONCLUSIONS: The T-type Ca(2+) channel may have dual roles in generating spontaneous excitation in detrusor smooth muscles. First, activity of these channels may account for the preceding depolarizations that lead to action potentials. Second, Ca(2+) influx through T-type Ca(2+) channels may couple functionally to SK channels, contributing to the stability of the resting membrane potential in detrusor smooth muscle. Thus, pharmacological manipulation of T-type Ca(2+) channels in detrusor smooth muscles could be of potential value for treating the overactive bladder. 相似文献
20.
N.J.M. Rijkhoff H. Wijkstra P.E.V. Van Kerrebroeck F.M.J. Debruyne 《Neurourology and urodynamics》1997,16(1):39-53
Evacuation of urine in paraplegics without the need for catheters would be possible when voiding could be induced by eliciting a bladder contraction. A challenging option to obtain detrusor contraction is electrical stimulation of the detrusor muscle or its motor nerves. This article reviews the 4 possible stimulation sites where stimulation would result in a detrusor contraction: the bladder wall, the pelvic nerves, the sacral roots, and the spinal cord. With respect to electrode application, sacral root stimulation is most attractive. However, in general, sacral root stimulation results in simultaneous activation of both the detrusor muscle and the urethral sphincter, leading to little or no voiding. Several methods are available to overcome the stimulation-induced detrusor-sphincter dyssynergia and allow urine evacuation. These methods, including poststimulus voiding, fatiguing of the sphincter, blocking pudendal nerve transmission, and selective stimulation techniques that allow selective detrusor activation by sacral root stimulation, are reviewed in this paper. 相似文献