Characterization of the membrane conductance changes underlying the apamin-resistant NANC inhibitory junction potential in the guinea-pig proximal and distal colon

Watson, Michael J.; Lang, Richard J; Bywater, Robert A.R.; Taylor, Grahame S.

doi:10.1016/0165-1838(96)00024-0

Cited by 23 publications

(39 citation statements)

References 40 publications

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“…However, our previous studies indicate that NANC relaxation mediated by pituitary adenylate cyclase activating peptide (PACAP) in the distal colon of Wistar‐ST rats is associated with SK channels (Kishi et al ., 1996; Takeuchi et al ., 1999). Nitric oxide‐mediated NANC relaxation was also suggested to be associated with the SK channels in the various tissue preparations (He & Goyal, 1993; Matsuyama et al ., 1999; Watson et al ., 1996; Keef et al ., 1993). These results indicate that the NANC relaxant mediator which is associated with SK channels differs among regions of the gastrointestinal tract and species of animals.…”

Section: Discussionmentioning

confidence: 99%

A possible role of neurotensin in NANC relaxation of longitudinal muscle of the jejunum and ileum of Wistar rats

Yamaji

Ohta

Yamazaki

et al. 2002

British J Pharmacology

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1 The mediators of nonadrenergic, noncholinergic (NANC) relaxation in longitudinal muscle of the jejunum and ileum of Wistar rats were examined in vitro. 2 Treatment of the jejunal and ileal segments with a-chymotrypsin resulted in decreases in the NANC relaxations induced by electrical ®eld stimulation (EFS) by about one half. 3 The NANC relaxations were also decreased by about one half after the segments had been desensitized to neurotensin. A neurotensin receptor antagonist, SR48692 (10 mM) inhibited the NANC relaxation by 56 and 34% in the jejunal and ileal segments, respectively. 4 An inhibitor of small conductance Ca 2+ -activated K + channel (SK channel), apamin (100 nM) also inhibited the NANC relaxation by 83 and 63%, respectively. Exogenous neurotensin-induced relaxations of the two segments were abolished by apamin. 5 In the ileal segments, N G -nitro-L-arginine (L-NOARG, 100 mM), inhibited the NANC relaxation by 43%. L-NOARG, but not apamin, further inhibited the relaxation which persisted after the desensitization to neurotensin. Apamin with SR48692 inhibited the relaxation only to the same extent as apamin alone. 6 EFS induced inhibitory junction potentials (i.j.ps) in the longitudinal muscle cells of the ileum. I.j.ps consisted of a rapid and a delayed phase. L-NOARG signi®cantly inhibited only the delayed phase. 7 EFS induced only a rapid i.j.ps in the jejunum. SR48692 and apamin inhibited the i.j.ps. 8 These ®ndings suggest that neurotensin and unknown substance(s) mediate NANC relaxation via SK channels in the jejunum of Wistar rats, and that neurotensin via SK channels and nitric oxide not via SK channels separately mediate the relaxation in the ileum.

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Section: Discussionmentioning

confidence: 99%

A possible role of neurotensin in NANC relaxation of longitudinal muscle of the jejunum and ileum of Wistar rats

Yamaji

Ohta

Yamazaki

et al. 2002

British J Pharmacology

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“…Zagorodnyuk & Maggi, 1994, Watson et al, 1996 and the hyperpolarizations to NC or NO, but had no effect on the hyperpolarizations to SNP ( Figure 5) or 8-bromo-cyclic GMP (Kitamura et al, 1993). NC and NO also appeared to be directly activating 'SK' channels as the time to peak and maximal amplitude of the hyperpolarizations to NO and NC were unaffected by wo-contoxin GVIA or L-NOARG and methylene blue, blockers of neurally-released NO and cytosolic guanylyl cyclase respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, membrane hyperpolarization itself induces voltage-dependent changes in the membrane conductance which masks the conductance changes during the NANC ij.p. (Watson et al, 1996) and NO donor hyperpolarizations.…”

Section: Discussionmentioning

confidence: 99%

Effects of nitric oxide (NO) and NO donors on the membrane conductance of circular smooth muscle cells of the guinea‐pig proximal colon

Watson

Bywater

Taylor

et al. 1996

British J Pharmacology

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1 The membrane conductance changes underlying the membrane hyperpolarizations induced by nitric oxide (NO), S-nitroso-L-cysteine (NC) and sodium nitroprusside (SNP) were investigated in the circular smooth muscle cells of the guinea-pig proximal colon, by use of standard intracellular microelectrode recording techniques.2 NO (1%), NC (2.5-25 AM) and SNP (1-1000 FM) induced membrane hyperpolarization in a concentration-dependent manner, the hyperpolarizations to NO and NC developing more rapidly than those to SNP. The slower-developing responses to SNP were mimicked by the membrane permeable analogue of guanosine 3':5' cyclic-monophosphate (cyclic GMP), 8-bromo-cyclic GMP (500 AM), and by isoprenaline (10 AM).3 The hyperpolarizations to NC and SNP were reduced in a low Ca2" (0.25 mM) saline and upon the addition of haemoglobin (20 AM), but were not effected by NG-nitro-L-arginine (L-NOARG) (100 AM) or cw-conotoxin GVIA (100 nM). The hyperpolarizations to SNP were also significantly reduced by methylene blue (50 AM). However, TEA (5-15 mm) reduced the membrane hyperpolarizations to SNP (10 AM) and isoprenaline (10 AM) in a concentration-dependent manner. The hyperpolarization to isoprenaline (10 AM) remaining in the presence of 15 mm TEA was blocked by ouabain (10 M). 5 The amplitude of electrotonic potentials (1 s duration) elicited during NO donor hyperpolarizations were little changed or only slightly reduced (5-25%). However, the amplitude of the electrotonic potentials elicited during maintained electrically-induced hyperpolarizations of similar amplitude were significantly increased (30-150%), suggesting that the non-linear membrane properties of the proximal colon partially mask an increase in membrane conductance elicited during the NO donor hyperpolarizations. 6 Membrane hyperpolarization in the presence of an NO donor, 8-bromo-cyclic GMP, isoprenaline, or upon application of a maintained hyperpolarizing electrical current, often evoked oscillations of the membrane potential. These oscillations were prevented by Cs' (1 mM). 7 These results indicate that NO and NC hyperpolarize the circular muscle of the proximal colon by activating at least two TEA-resistant membrane K+ conductances, one of which is sensitive to apamin blockade. The K+ conductance increases activated by SNP or 8-bromo-cyclic GMP were little effected by apamin, perhaps suggesting a common mechanism. In contrast, the hyperpolarization to isoprenaline appears to involve the activation of TEA-sensitive Ca2+-activated K+ ('BK') channels, as well as a Na:K ATPase. Finally, the 'background' membrane conductance of the circular muscle cells of the proximal colon decreased upon membrane hyperpolarization to reveal oscillations of the membrane potential which may well represent 'pacemaker' or 'slow wave' activity.

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“…Release of NO during the same period results in a smaller amplitude and longer-duration hyperpolarization phase that can outlast the fast phase of the IJP by several times. The fast hyperpolarization arises from activation of apamin-sensitive, small-conductance Ca 2ϩ -activated K ϩ channels (SK) (14), and the slow phase of the IJP is due to NOdependent stimulation of cyclic GMP production, activation of protein kinase G, and activation of NO-dependent K conductance(s) (5,26,28,29). In most preparations, repolarization from the IJP results in a depolarization phase (rebound excitation) through activation of chloride (10) and nonselective cation conductance (NSCC) (11, 12).…”

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confidence: 99%

Mechanism of active repolarization of inhibitory junction potential in murine colon

Baker

Mutafova‐Yambolieva

Monaghan

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Mechanism of active repolarization of inhibitory junction potential in murine colon. Am J Physiol Gastrointest Liver Physiol 285: G813-G821, 2003; 10.1152/ajpgi. 00115.2003.-Enteric inhibitory responses in gastrointestinal (GI) smooth muscles involve membrane hyperpolarization that transiently reduce the excitability of GI muscles. We examined the possibility that an active repolarization mechanism participates in the restoration of resting membrane potential after fast inhibitory junction potentials (IJPs) in the murine colon. Previously, we showed these cells express a voltage-dependent nonselective cation conductance (NSCC) that might participate in active repolarization of IJPs. Colonic smooth muscle cells were impaled with microelectrodes and voltage responses to nerve-evoked IJPs, and locally applied ATP were recorded. Ba 2ϩ (500 M), a blocker of the NSCC, slowed the rate of repolarization of IJPs. We also tested the effects of Ba 2ϩ , Ni 2ϩ , and mibefradil, all blockers of the NSCC, on responses to locally applied ATP. Spritzes of ATP caused transient hyperpolarization, and the durations of these responses were significantly increased by the blockers of the NSCC. We considered whether NSCC blockers might affect ATP metabolism and found that Ni 2ϩ decreased ATP breakdown in colonic muscles. Mibefradil had no effect on ATP metabolism. Because both Ni 2ϩ and mibefradil had similar effects on prolonging responses to ATP, it appears that restoration of resting membrane potential after ATP spritzes is not primarily due to ATP metabolism. Neurally released enteric inhibitory transmitter and locally applied ATP resulted in transient hyperpolarizations of murine colonic muscles. Recovery of membrane potential after these responses appears to involve an active repolarization mechanism due to activation of the voltage-dependent NSCC expressed by these cells. gastrointestinal motility; adenosine 5Ј-triphosphate; voltagedependent nonselective cation current GASTROINTESTINAL (GI) motility is orchestrated by the enteric nervous system activating and inhibiting GI muscles in orderly patterns. The inhibitory component of neuromuscular regulation comes from release of several neurotransmitter substances, including ATP, NO, and peptides (4, 10, 21). In GI muscles such as human, murine, and guinea pig colon, release of ATP during nerve stimulation evokes a fast inhibitory junction potential (IJP), which transiently takes the membrane potentials of smooth muscle cells toward the equilibrium potential for the K ϩ ionic gradient (hyperpolarization) (8,22). Release of NO during the same period results in a smaller amplitude and longer-duration hyperpolarization phase that can outlast the fast phase of the IJP by several times. The fast hyperpolarization arises from activation of apamin-sensitive, small-conductance Ca 2ϩ -activated K ϩ channels (SK) (14), and the slow phase of the IJP is due to NOdependent stimulation of cyclic GMP production, activation of protein kinase G, and activation of NO-dependent K conductance(s) (5,...

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Characterization of the membrane conductance changes underlying the apamin-resistant NANC inhibitory junction potential in the guinea-pig proximal and distal colon

Cited by 23 publications

References 40 publications

A possible role of neurotensin in NANC relaxation of longitudinal muscle of the jejunum and ileum of Wistar rats

A possible role of neurotensin in NANC relaxation of longitudinal muscle of the jejunum and ileum of Wistar rats

Effects of nitric oxide (NO) and NO donors on the membrane conductance of circular smooth muscle cells of the guinea‐pig proximal colon

Mechanism of active repolarization of inhibitory junction potential in murine colon

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