Electrical responses of gastric smooth muscles in streptozotocin-induced diabetic rats

1997 ◽  
Vol 272 (1) ◽  
pp. G77-G83 ◽  
Author(s):  
L. Xue ◽  
H. Suzuki

Electrical responses of gastric smooth muscles produced by transmural nerve stimulation, acetylcholine, norepinephrine, or K-free solution were investigated in streptozotocin-induced diabetic rats, using intracellular microelectrode techniques. In muscles from diabetic rats, 1) the resting membrane potential remained unchanged, 2) slow waves disappeared or were markedly reduced in amplitude, 3) the excitatory junction potential was absent, and in most cases only an inhibitory junction potential of reduced amplitude was elicited, 4) the amplitude of the hyperpolarization generated after superfusion with K-free solution was reduced, 5) the sensitivity of the acetylcholine-induced membrane depolarization was increased, and 6) the norepinephrine-induced hyperpolarization was reduced because of functional loss of alpha- and beta-adrenoceptors. Thus diabetes mellitus caused functional impairment of neuromuscular transmission, reduced the maximum activity of the electrogenic pump, increased the sensitivity of muscarinic receptors, reduced the sensitivity of adrenoceptors, and reduced the myogenic activity in gastric smooth muscles. These alterations in the properties of smooth muscle may be involved in the diabetes-induced gastroparesis.

1995 ◽  
Vol 269 (6) ◽  
pp. H2031-H2038 ◽  
Author(s):  
J. Xia ◽  
T. L. Little ◽  
B. R. Duling

We have previously shown that conducted vasomotor responses follow patterns that are consistent with a passive spread of electrical current along the length of the arterioles [(Xia and Duling, Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H2022-H2030, 1995]. In this study, we define the cells through which the current flows. Isolated arterioles of hamster cheek pouch were used. The mean resting membrane potential (RMP) for randomly sampled arteriolar cells was -67 mV. When cell types were identified by dye injection, the RMPs were -68 and -67 mV for smooth muscle (SM) and endothelium (EC), respectively. Pulses of KCl induced transient, monophasic depolarizations at the site of stimulation (local), which were conducted decrementally along the length of the arteriole over several millimeters. During electrical conduction, three patterns of responses could be observed, but identical patterns of the conducted electrical responses were always observed in SM and EC. Phenylephrine stimulation also caused transient local and conducted depolarizations in both SM and EC. As with KCl stimuli, shapes of conducted electrical responses were identical in records made in both cell types. The results suggest that SM and EC are electrically coupled both homocellularly and heterocellularly.


1987 ◽  
Vol 65 (10) ◽  
pp. 2104-2109
Author(s):  
Neil D. Berman ◽  
Richard I. Ogilvie ◽  
James E. Loukides

The persistence of cellular electropharmacologic effects of mexiletine on canine Purkinje fibers was studied utilizing standard microelectrode techniques and two different protocols. In the first, the tissue was exposed to hypoxic perfusion before and 30 min after perfusion with one of the following: mexiletine hydrochloride 6.25 μM solution, mexiletine hydrochloride 12.5 μM solution, or drug-free Tyrode's solution. With the higher concentration of mexiletine, depression of the maximal upstroke velocity [Formula: see text] persisted 30 min after drug washout and subsequent exposure to hypoxia did not result in the anticipated shortening of action potential duration but did prevent the restoration of normal [Formula: see text]. After perfusion with the lower concentration of mexiletine, [Formula: see text] was not depressed and hypoxic action potential duration shortening was not prevented. In the second protocol, Purkinje fibers were perfused with 12.5 μM mexiletine hydrochloride solution and then exposed to hypoxia after 15, 30,45, or 60 min of perfusion with drug-free solution. Depression of maximal upstroke velocity and shortening of action potential duration persisted during washout, returning to control values by 45 min, although mexiletine was not detectable in the tissue bath after 10 min of washout. Hypoxia initiated at 15 or 30 min of washout failed to produce the anticipated shortening of action potential duration. At 45 and 60 min, action potential duration was shortened by hypoxia. We concluded that mexiletine depression of [Formula: see text] and shortening of action potential duration may persist in the absence of drug. Further shortening of action potential duration in response to hypoxia is prevented during this period. The persistence of [Formula: see text] depression is prolonged by hypoxia.


Author(s):  
OR Johnson-Ajinwo ◽  
◽  
Kuebari Penuel Berebari ◽  

Background: Diabetes Mellitus (DM), is a malignant disease that has impacted the globe in astronomical proportions. Chronic hyperglycemia is a major condition suffered by patients with DM. Currently, the cost of managing DM is highly exorbitant and poses a significant obstacle to many living with the disease in developing countries. Thus, the need for affordable alternatives with optimum potency and minimal side effects is justified. Historically, Annona muricata is one plant that is used in the treatment of DM and a host of other ailments. Rutidea parviflora has been used in combination with other plants in the treatment of DM by some ethnic groups. The aim of this study is to investigate the anti-diabetic activities of these plants. Method: The anti-diabetic activities of aqueous and organic extracts of Annona muricata (leaves), and Rutidea parviflora (root bark) at 200 mg/kg and 400 mg/kg, were screened for their anti-diabetic activities in normoglycemic and alloxan-induced diabetic rats (150-200 g) at 1h, 2h, 4h, 6h, 8h, and the 12th hour. DMSO (0.3 ml of 33.3% v/v stock) and Glibenclamide 10 mg/kg were administered to the control and reference groups respectively. Result: Organic extracts of A. muricata at 400 mg/kg significantly decreased FBGL in both normoglycemic and hyperglycemic groups by 65.9% and 62.1% respectively (P<0.05). R. parviflora leaves extracts showed less activity. However, it had relatively short acting activity (maximum activity at the 4th hour). In each case, the organic extracts performed better than the aqueous extracts. Conclusion: A. muricata has potentials for the treatment of DM, and merits further research to support the plant’s therapeutic application. R. parviflora may offer some beneficial effect, and possibly boost the potency of A. muricata by synergistic activity when co-administered.


2000 ◽  
Vol 278 (5) ◽  
pp. G725-G733 ◽  
Author(s):  
L. Xue ◽  
G. Farrugia ◽  
J. H. Szurszewski

Intracellular recordings were made from the circular smooth muscle cells of the canine jejunum to study the effect of exogenous ATP and to compare the ATP response to the nonadrenergic, noncholinergic (NANC) inhibitory junction potential (IJP) evoked by electrical field stimulation (EFS). Under NANC conditions, exogenous ATP evoked a transient hyperpolarization (6.5 ± 0.6 mV) and EFS evoked a NANC IJP (17 ± 0.4 mV). ω-Conotoxin GVIA (100 nM) and a low-Ca2+, high-Mg2+ solution abolished the NANC IJP but had no effect on the ATP-evoked hyperpolarization. The ATP-evoked hyperpolarization and the NANC IJP were abolished by apamin (1 μM) and N G-nitro-l-arginine (100 μM). Oxyhemoglobin (5 μM) partially (38.8 ± 5.5%) reduced the amplitude of the NANC IJP but had no effect on the ATP-evoked hyperpolarization. Neither the NANC IJP nor the ATP-evoked hyperpolarization was affected by P2 receptor antagonists or agonists, including suramin, reactive blue 2, 1-( N, O-bis-[5-isoquinolinesulfonyl]- N-methyl-l-tyrosyl)-4-phenylpiperazine, pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid, α,β-methylene ATP, 2-methylthioadenosine 5′-triphosphate tetrasodium salt, and adenosine 5′- O-2-thiodiphosphate. The data suggest that ATP evoked an apamin-sensitive hyperpolarization in circular smooth muscle cells of the canine jejunum via local production of NO in a postsynaptic target cell.


1982 ◽  
Vol 242 (1) ◽  
pp. C59-C64 ◽  
Author(s):  
C. A. Colton ◽  
J. S. Colton

Diamide[diazine-dicarboxylic acid-bis(dimethylamide)], a thiol-oxidizing agent, has both pre- and postsynaptic actions on the glutaminergic neuromuscular junction of the lobster walking leg. Postsynaptically, diamide produced an increase in the response to exogenously applied glutamate, whereas the effect of diamide on presynaptic transmitter release involved two major changes: 1) a decrease in excitatory junction potential amplitude and 2) an increase in miniature junction potential frequency. Short-term facilitation also decreased. Equilibration with 1,4-dithiothreitol (a sulfhydryl-reducing agent) reversed the decline in excitatory junction potential frequency, and the fall in short-term facilitation. The miniature junction potential frequency increase induced by diamide was independent of external Ca2+, as diamide in a Ca2+-free solution produced a similar response to that in a Ca2+-containing solution. We propose that the action of diamide on transmitter release is similar to the action of polyvalent cations, i.e., diamide has two sites of action, a blockade of inward Ca2+ flux and an increased release of Ca2+ inside the terminal.


1985 ◽  
Vol 107 (3) ◽  
pp. 397-401 ◽  
Author(s):  
P. A. McGrath ◽  
J. R. Bourke ◽  
G. J. Huxham ◽  
S. W. Manley

ABSTRACT Cultured porcine thyroid cells, maintained in the differentiated state by dibutyryl cyclic AMP, responded to serotonin (5-HT; 10 nmol/l to 1 μmol/l) with a depolarization of the membrane potential, but did not respond to histamine (100 μmol/l) or dopamine (1 μmol/l). The resting membrane potential of these cells was about − 71 mV, maximal concentrations of 5-HT (1 μmol/l) inducing a depolarization to approximately −53 mV. Methysergide or phenoxybenzamine, but not propranolol, abolished the response to 5-HT. Sensitivity to 5-HT was reduced by previous exposure of cultures to TSH, the β-adrenoceptor agonist salbutamol or 5-HT itself. J. Endocr. (1985) 107, 397–401


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