Expression and function of KCNH2 (HERG) in the human jejunum

A. M. Farrelly, S. Ro, B. P. Callaghan, M. A. Khoyi, Neal Fleming, B. Horowitz, K. M. Sanders, K. D. Keef

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Previous studies suggest that ether-a-go-go related gene (ERG) KCNH2 potassium channels contribute to the control of motility patterns in the gastrointestinal tract of animal models. The present study examines whether these results can be translated into a role in human gastrointestinal muscles. Messages for two different variants of the KCNH2 gene were detected: KCNH2 V1 human ERG (HERG) (28) and KCNH2 V2 (HERGUSO) (13). The amount of V2 message was greater than V1 in both human jejunum and brain. The base-pair sequence that gives rise to domains S3-S5 of the channel was identical to that previously published for human KCNH2 V1 and V2. KCNH2 protein was detected immunohistochemically in circular and longitudinal smooth muscle and enteric neurons but not in interstitial cells of Cajal. In the presence of TTX (10-6 M), atropine (10-6 M). and L-nitroarginine (10-4 M) human jejunal circular muscle strips contracted phasically (9 cycles/min) and generated slow waves with superimposed spikes. Low concentrations of the KCNH2 blockers E-4031 (10-8 M) and MK-499 (3 × 10-8 M) increased phasic contractile amplitude and the number of spikes per slow wave. The highest concentration of E-4031 (10-6 M) produced a 10-20 mV depolarization, eliminated slow waves, and replaced phasic contractions with a small tonic contracture. E-4031 (10-6 M) did not affect [14C]ACh release from enteric neurons. We conclude that KCNH2 channels play a fundamental role in the control of motility patterns in human jejunum through their ability to modulate the electrical behavior of smooth muscle cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number6 47-6
StatePublished - Jun 1 2003


  • Gastrointestinal
  • Membrane potential
  • Motility
  • Potassium channels
  • Smooth muscle

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology


Dive into the research topics of 'Expression and function of KCNH2 (HERG) in the human jejunum'. Together they form a unique fingerprint.

Cite this