Localization of calcium channels of the L-type in human epicardial arteries: a light microscope autoradiographic...

The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.