ERG K+ currents regulate pacemaker activity in ICC

Yaohui Zhu, Catherine M. Golden, Jing Ye, Xuan Yu Wang, Hamid I. Akbarali, Jan D. Huizinga

Research output: Contribution to journalArticle

Abstract

Ether-à-go-go-related gene (ERG) K channels have been implicated in the generation of pacemaker activities in the heart. To study the presence and function of ERG K channels in the pacemaker cells of the small intestine [the interstitial cells of Cajal (ICC)], a combination of patch-clamp techniques, tissue and live cell immunohistochemistry, RT-PCR, and in vitro functional studies were performed. Nonenzymatically isolated ICC in culture were identified by vital staining and presence of rhythmic inward currents. RT-PCR showed the presence of ERG mRNA in the intestinal musculature, and immunohistochemistry on tissue and cultured cells demonstrated that protein similar to human ERG was concentrated on ICC in the Auerbach's plexus region. Whole cell ERG K+ currents were evoked on hyperpolarization from 0 mV (but not from -70 mV) up to -120 mV and showed strong inward rectification. The currents were inhibited by E-4031, cisapride, La3+, and Gd 3+ but not by 50 μM Ba2+. The ERG K+ inward current had a typical transient component with fast activation and inactivation kinetics followed by significant steady-state current. E-4031 also inhibited tetraethylammonium (TEA)-insensitive outward current indicating that the ERG K+ current is operating at depolarizing potentials. In contrast to TEA, blockers of the ERG K+ currents caused marked increase in tissue excitability as reflected by an increase in slow-wave duration and an increase in superimposed action potential activity. In summary, ERG K channels in ICC contribute to the membrane potential and play a role in regulation of pacemaker activity of the small intestine.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume285
Issue number6 48-6
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Interstitial Cells of Cajal
Tetraethylammonium
Small Intestine
Immunohistochemistry
Cisapride
Myenteric Plexus
Polymerase Chain Reaction
Patch-Clamp Techniques
Ether
Membrane Potentials
Action Potentials
Cultured Cells
Staining and Labeling
Messenger RNA
Genes
Proteins
E 4031

Keywords

  • Interstitial cells of Cajal
  • Motility
  • Potassium channels
  • Small intestine

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Zhu, Y., Golden, C. M., Ye, J., Wang, X. Y., Akbarali, H. I., & Huizinga, J. D. (2003). ERG K+ currents regulate pacemaker activity in ICC. American Journal of Physiology - Gastrointestinal and Liver Physiology, 285(6 48-6).

ERG K+ currents regulate pacemaker activity in ICC. / Zhu, Yaohui; Golden, Catherine M.; Ye, Jing; Wang, Xuan Yu; Akbarali, Hamid I.; Huizinga, Jan D.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 285, No. 6 48-6, 12.2003.

Research output: Contribution to journalArticle

Zhu, Y, Golden, CM, Ye, J, Wang, XY, Akbarali, HI & Huizinga, JD 2003, 'ERG K+ currents regulate pacemaker activity in ICC', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 285, no. 6 48-6.
Zhu, Yaohui ; Golden, Catherine M. ; Ye, Jing ; Wang, Xuan Yu ; Akbarali, Hamid I. ; Huizinga, Jan D. / ERG K+ currents regulate pacemaker activity in ICC. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2003 ; Vol. 285, No. 6 48-6.
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