Are dipyridamole (sensitive) calcium channels present in esophageal smooth muscle?

Calcium (Ca2+) entry from the extra-cellular space into the cytoplasm through voltage-dependent Ca2+ channels, specifically dipyridamole (DHP) sensitive ones (L-type), control a variety of biological processes, including excitation-contraction coupling in vascular and GI muscle cells. It has also been proposed that these channels may control esophageal contractility. However, DHP-sensitive Ca2+ channels in esophagus have not been well characterized biochemically. Thus, it is not known if these channels are similar in number or affinity to those in vascular or neural tissues--organs for which clinical use of calcium channel blockers has been successful. Thus, the purpose of this study was to identify and characterize DHP-sensitive calcium channels in esophagus and compare them to vascular, neural, and other GI tissues.

We carried out in vitro receptor binding assays on lower esophageal muscle homogenates, gastric and intestinal and colonic homogenates, and aortic muscle homogenates from ca; and on brain homogenates from rat. We used a radio-labeled dihydropyridine derivative [3H]nitrendipine, to label these sites and co-administration of unlabeled nimodipine to define specific binding.

As expected, ligand binding to L-type Ca2+ channels in aortic vascular smooth muscle and brain was readily detectable: brain, Bmax=252 fmol/mg protein, Kd=0.88 nM; aorta, Bmax=326 fmol/mg protein, Kd=0.84 nM. For esophagus (Bmax=97; Kd=0.73) and for other GI tissues, using the same assay conditions, we detected a smaller signal, suggesting that L-type Ca2+ channels are present in lower quantities.

L-type Ca2+ channel are present in esophagus and in other GI muscles, their affinity is similar, but their density is relatively sparse. These findings are consistent with the relatively limited success that has been experienced clinically in the use of calcium channel blockers for treatment of esophageal dysmotility.