LOCALIZATION OF CALCIUM CHANNELS OF THE L-TYPE IN HUMAN EPICARDIAL ARTERIES - A LIGHT-MICROSCOPE AUTORADIOGRAPHIC STUDY

The anatomical localization of Ca2+ channels of the L-type was analyze d in sections of the human right and anterior interventricular coronar y arteries by using in vitro light microscope autoradiography associat ed with radioligand binding techniques. [H-3]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronar y arteries was time-, temperature- and concentration-dependent. Analys is of binding isotherms revealed a dissociation constant value of abou t 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 f or the anterior interventricular branch. The pharmacological profile o f [H-3]nicardipine binding to sections of human coronary arteries was consistent;with the labelling of Ca2+ channels of the L-type. Dihydrop yridine derivatives were the most powerful competitors of [H-3]nicardi pine binding, whereas phenylalkilamines, benzothiazepine or non-select ive channel modulators were weak competitors or ineffective. Light mic roscope autoradiography revealed the highest density of [3H]nicardipin e binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cel ls. A lower accumulation of the radioligand occurred in the tunica adv entitia, whereas no specific binding was found in the tunica intima. S tudy of the localization of Ca2+ channels in sections of human coronar y arteries may contribute to a better understanding of the mechanism o f the marked coronary dilatory activity elicited by Ca2+ antagonists d emonstrable in both in vitro preparations and in vivo.