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

Yaohui Zhu, Jing Ye, Jan D. Huizinga

Research output: Contribution to journalArticle

Abstract

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 (ICTL) 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 ICTL 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 (τ = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased ICTL. Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of ∼38 pS. In summary, ICC generate a ICTL on depolarization through an intermediate-conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Interstitial Cells of Cajal
Clotrimazole
Calcium-Activated Potassium Channels
Nitroprusside
Membrane Potentials
Calcium
Nitric Oxide Donors
Ether
Motor Activity

Keywords

  • Calcium
  • Intermediate conductance
  • Inwardly rectifying potassium channels
  • Patch clamp

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

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title = "Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal",
abstract = "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 (ICTL) 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 ICTL 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-{\`a}-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 (τ = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased ICTL. Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of ∼38 pS. In summary, ICC generate a ICTL on depolarization through an intermediate-conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability.",
keywords = "Calcium, Intermediate conductance, Inwardly rectifying potassium channels, Patch clamp",
author = "Yaohui Zhu and Jing Ye and Huizinga, {Jan D.}",
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language = "English (US)",
volume = "292",
journal = "American Journal of Physiology",
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T1 - Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal

AU - Zhu, Yaohui

AU - Ye, Jing

AU - Huizinga, Jan D.

PY - 2007/6

Y1 - 2007/6

N2 - 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 (ICTL) 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 ICTL 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 (τ = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased ICTL. Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of ∼38 pS. In summary, ICC generate a ICTL on depolarization through an intermediate-conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability.

AB - 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 (ICTL) 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 ICTL 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 (τ = 88 ms), showed little time-dependent inactivation, and exhibited a deactivation time constant of 38 ms. The nitric oxide donor sodium nitroprusside (SNP) increased ICTL. Single-channel activity, activated by calcium and SNP, was inhibited by CTL, with a single-channel conductance of ∼38 pS. In summary, ICC generate a ICTL on depolarization through an intermediate-conductance calcium-activated K channel that regulates pacemaker activity and ICC excitability.

KW - Calcium

KW - Intermediate conductance

KW - Inwardly rectifying potassium channels

KW - Patch clamp

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