• aganglionic bowel;
  • Hirschsprung’s disease, smooth muscle


Background  Studies on animal models of Hirschsprung’s disease (HD) suggest that L-type Ca2+ channels are down-regulated in the aganglionic bowel segment, however, this has yet to be confirmed in HD patients. The objective of this study was to test the hypothesis that L-type Ca2+ current density is decreased in smooth muscle cells (SMC) obtained from the aganglionic bowel segment of patients with HD in comparison with those from the ganglionic segment.

Methods  Smooth muscle cells were freshly isolated from colon samples obtained from HD patients undergoing pull-through surgery. L-type Ca2+ currents were recorded using the perforated patch configuration of the whole cell voltage clamp technique and the expression levels of CACNA1C transcripts (which encode L-type Ca2+ channels) in the ganglionic and aganglionic bowel segments were compared using real-time quantitative PCR.

Key Results  All SMC displayed robust currents that had activation/inactivation kinetics typical of L-type Ca2+ current, were inhibited by nifedipine and enhanced by the L-type Ca2+ channel agonists FPL 64176 and Bay K 8644. Moreover, FPL 64176 activated currents were also inhibited by nifedipine. However, there was no significant difference in L-type Ca2+ current density, CACNA1C subunit expression or sensitivity to the pharmacological agents noted above, between SMC isolated from the ganglionic and aganglionic regions of the HD colon.

Conclusions & Inferences  In contrast to studies on genetic animal models of HD, L-type Ca2+ currents are not down-regulated in the aganglionic bowel segment of HD patients and are therefore unlikely to account for the impaired colonic peristalsis observed in these patients.