Blockage of the HERG human cardiac K+ channel by the gastrointestinal prokinetic agent cisapride

Saeed Mohammad, Zhengfeng Zhou, Qiuming Gong, Craig T. January

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


Cisapride, a gastrointestinal prokinetic agent, is known to cause long Q-T syndrome and ventricular arrhythmias. The cellular mechanism is not known. The human ether-a-go-go-related gene (HERG), which encodes the rapidly activating delayed rectifier K+ current and is important in cardiac repolarization, may serve as a target for the action of cisapride. We tested the hypothesis that cisapride blocks HERG. The whole cell patch-clamp recording technique was used to study HERG channels stably expressed heterologously in HEK293 cells. Under voltage-clamp conditions, cisapride block of HERG is dose dependent with a half-maximal inhibitory concentration of 6.5 nM at 22°C (n = 25 cells). Currents rapidly recovered with drug washout. The onset of block by cisapride required channel activation indicative of open or inactivated state blockage. Block o HERG with cisapride after channel activation was voltage dependent. At -20 mV, 10 nM cisapride reduced HERG tail-current amplitude by 5%, whereas, at +20 mV, the tail- current amplitude was reduced by 45% (n = 4 cells). At -20 and +20 mV, 100 nM cisapride reduced tail-current amplitude by 66 and 90%, respectively. We conclude that cisapride is a potent blocker of HERG channels expressed in HEK293 cells. This effect may account for the clinical occurrence of Q-T prolongation and ventricular arrhythmias observed with cisapride.

Original languageEnglish (US)
Pages (from-to)H2534-H2538
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5 42-5
StatePublished - 1997
Externally publishedYes


  • Gastrointestinal motility
  • Potassium channels
  • Q-T interval
  • Rapidly activating delayed-rectifier potassium current
  • Torsades de pointes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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