Ghrelin and Motilin Control Gut Pacemaker Rhythms in Mouse Intestines

The gastrointestinal (GI) tract relies on rhythmic contractions for digestion and nutrient absorption, a process known as motility. These contractions are orchestrated by specialized cells called Interstitial Cells of Cajal (ICCs), which act as electrical pacemakers, generating slow wave potentials. Hormones like ghrelin and motilin are known to influence GI motility, but the precise cellular and ionic mechanisms by which they modulate these ICC pacemaker potentials remained unclear.

The study revealed that both Ghrelin and Motilin significantly altered ICC pacemaker activity. Ghrelin application led to a robust increase in pacemaker frequency by 34.8% (p<0.01) and an increase in amplitude by 21.5% (p<0.05) compared to control. Motilin similarly enhanced pacemaker frequency by 28.1% (p<0.01) and amplitude by 18.7% (p<0.05). Further investigation using specific antagonists indicated that Ghrelin's effects were primarily mediated through the activation of Ca2+ channels and inhibition of K+ channels, while Motilin's actions involved similar Ca2+ channel modulation. > The most significant finding was that Ghrelin's effects on ICC pacemaker frequency were largely dependent on the activation of Ca2+ influx via L-type calcium channels, leading to a 2.5-fold increase in the rate of depolarization.