Potassium channel diversity within the muscular components of the feline lower esophageal sphincter

Salapatek, Anne Marie; Ji, Junzhi; Muinuddin, Ahmad; Diamant, Nicholas E.

doi:10.1139/y04-090

Cited by 7 publications

(5 citation statements)

References 49 publications

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“…Nitric oxide may act directly or through increase in intracellular calcium (25). It is not uncommon that K channels can be modified by nitric oxide (3,28,30). It is not uncommon that K channels can be modified by nitric oxide (3,28,30).…”

Section: Discussionmentioning

confidence: 99%

Clotrimazole-sensitive K⁺ currents regulate pacemaker activity in interstitial cells of Cajal

Zhu

Huizinga

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Interstitial cells of Cajal (ICC) are pacemaker cells for gut peristaltic motor activity. Compared with cardiac pacemaker cells, little is known about mechanisms that regulate ICC excitability. The objective of the present study was to investigate a potential role for clotrimazole (CTL)-sensitive K currents (I(CTL)) in the regulation of ICC excitability and pacemaker activity. ICC were studied in situ and in short-term culture by using the whole cell patch-clamp configuration. In situ, ICC exhibited spontaneous transient inward currents followed by transient outward currents. CTL blocked outward currents, thereby increasing the net inward currents, and depolarized ICC, thereby establishing CTL-sensitive channels as regulators of ICC pacemaker activity. In short-term culture, a I(CTL) was identified that showed increased conductance when depolarized from the resting membrane potential to 0 mV and subsequent inward rectification at further depolarized potentials. The I(CTL) markedly increased with increasing intracellular calcium and was insensitive to the ether-à-go-go-related K channel blocker E-4031 and the large-conductance calcium-activated K channel blocker iberiotoxin. I(CTL) contributed 3-9 nS to the whole cell conductance at 0 mV membrane potential under physiological conditions; it was fast activating (tau = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased I(CTL). Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of approximately 38 pS. In summary, ICC generate a I(CTL) on depolarization through an intermediate-conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability.

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Section: Discussionmentioning

confidence: 99%

Clotrimazole-sensitive K⁺ currents regulate pacemaker activity in interstitial cells of Cajal

Zhu

Huizinga

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In LES sling muscle, KCl caused sustained contractions at low and high concentrations that were abolished in the presence of nifedipine. Because the resting membrane potential in sling muscle is relatively less depolarized than the circular muscle (28), this contractile activity is likely due to membrane depolarization leading to activation of I Ca,L . However, in the more depolarized LES circular muscle, further depolarization with KCl (5-60 mM) caused rapid inhibition of tone that could be explained in at least two ways.…”

Section: Discussionmentioning

confidence: 99%

Regional differences in L-type Ca²⁺channel expression in feline lower esophageal sphincter

Muinuddin¹,

Kang²,

Gaisano³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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In humans and cats, muscle from the lower esophageal sphincter (LES) circular region exhibits greater spontaneous tone than LES sling muscle, whereas the sling muscle is much more responsive to cholinergic stimulation. Despite physiological and pharmacological evidence for the presence of L-type Ca2+ channel current (ICa,L) activity in LES circular muscle, the identity of this channel has not been demonstrated biochemically or electrophysiologically fingerprinted. Furthermore, there is no information on the channel's presence and role in the sling region of the LES. We hypothesized that regional differences in the expression of ICa,L between LES circular and sling muscles, if present, could contribute to the functional asymmetry observed within the LES. ICa,L expression was compared between circular and sling regions of the LES by Western blot analysis. The patch-clamp technique was used to study ICa,L. Muscle strip studies assessed ICa,L contribution to contractile activity. We found both protein expression of ICa,L and ICa,L density to be greater in LES circular muscle than sling muscle. ICa,L voltage- and time-dependent activation and inactivation curves were similar in cells from both regions. ICa,L blockade with nifedipine inhibited spontaneous tone and ACh-induced contractions only in circular muscle but was able to abolish depolarization (KCl)-induced contractions in both sling and circular muscles. In contrast, La3+ inhibited tone and ACh-induced contractions in muscles from both regions. Therefore, regional myogenic differences in ICa,L expression within the LES circular and sling muscle exist and provide one explanation for the differential contribution of sling and circular muscle to LES contractility.

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“…The circular muscle has significant spontaneous tone, whereas the sling muscle has little tone and is more responsive to cholinergic stimulation (30,37,38,47,51). Furthermore, these two muscles demonstrate differences in resting membrane potential, voltage-gated K ϩ and Ca 2ϩ channel current densities, and calcium handling (28,29,43). These differences provide for the likelihood that neural mediation of relaxation as well as maintenance of resting tone would also differ in sling and circular muscles.…”

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confidence: 99%

Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses

L’Heureux¹,

Muinuddin²,

Gaisano³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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The lower esophageal sphincter (LES) has a circular muscle component exhibiting spontaneous tone that is relaxed by nitric oxide (NO) and a low-tone sling muscle that contracts vigorously to cholinergic stimulation but with little or no evidence of NO responsiveness. This study dissected the responses of the sling muscle to nitrergic innervation in relationship to its cholinergic innervation and circular muscle responses. Motor responses were induced by electrical field stimulation (EFS; 1-30 Hz) of muscle strips from sling and circular regions of the feline LES in the presence of cholinergic receptor inhibition (atropine) or NO synthase inhibition [NG-nitro-L-arginine (L-NNA)+/-atropine]. This study showed the following. First, sling muscle developed less intrinsic resting tone compared with circular muscle. Second, with EFS, sling muscle contracted (most at 50% by 5 Hz. Third, on neural blockade with atropine or L-NNA+/-atropine, 1) sling muscle, although predominantly influenced by excitatory cholinergic stimulation, had a small neural NO-mediated inhibition, with no significant non-NO-mediated inhibition and 2) circular muscle, although little affected by cholinergic influence, underwent relaxation predominantly by neural release of NO and some non-NO inhibitory influence (at higher EFS frequency). Fourth, the sling, precontracted with bethanecol, could relax with NO and some non-NO inhibition. Finally, the tension range of both muscles is similar. In conclusion, sling muscle has limited NO-mediated inhibition to potentially augment or replace sling relaxation effected by switching off its cholinergic excitation. Differences within the LES sling and circular muscles could provide new directions for therapy of LES disorders.

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Potassium channel diversity within the muscular components of the feline lower esophageal sphincter

Cited by 7 publications

References 49 publications

Clotrimazole-sensitive K⁺ currents regulate pacemaker activity in interstitial cells of Cajal

Clotrimazole-sensitive K⁺ currents regulate pacemaker activity in interstitial cells of Cajal

Regional differences in L-type Ca²⁺channel expression in feline lower esophageal sphincter

Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses

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Potassium channel diversity within the muscular components of the feline lower esophageal sphincter

Cited by 7 publications

References 49 publications

Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal

Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal

Regional differences in L-type Ca2+channel expression in feline lower esophageal sphincter

Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses

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Product

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Clotrimazole-sensitive K⁺ currents regulate pacemaker activity in interstitial cells of Cajal

Clotrimazole-sensitive K⁺ currents regulate pacemaker activity in interstitial cells of Cajal

Regional differences in L-type Ca²⁺channel expression in feline lower esophageal sphincter