Functional importance of alpha adrenoceptor-mediated, D600-insensitive Ca++ entry in rabbit aorta

RK Hester

Department of Medical Pharmacology & Toxicology, College of Medicine, Texas A & M University, College Station.

Specific receptor-linked Ca++ entry (RLCa++E) was studied separately from Ca++ release and potential-dependent Ca++ entry (PDCa++E) in rabbit aorta after incubation in a Ca++-free solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid to bind trace levels of Ca++ and including methoxyverapamil (D600) (10(-5) M) to inhibit PDCa++E. Adding norepinephrine (NE) under these conditions resulted in a transient response which was attributed to Ca++ release from a limited cellular store. Subsequent addition of Ca++ results in a sustained contraction that was dependent upon the concentration of agonist and Ca++. This maintained response which by definition was insensitive to D600 was attributed to RLCa++E, was extensively relaxed or inhibited by nitroprusside or nitroglycerin and was partially relaxed by KCl or tetraethylammonium. Contractions due to RLCa++E alone equaled or exceeded the peak tension attained solely as a result of Ca++ release. At higher NE concentrations (greater than 10(- 7) M), RLCa++E provided sufficient Ca++ to attain and sustain maximal levels of developed tension without requiring any additional Ca++ from either PDCa++E or Ca++ release. This high flux capacity of these receptor-linked Ca++ channels may partially account for the relative insensitivity of contractile responses to these higher concentrations of NE to D600. The relative contribution of PDCa++E to the elevation of myoplasmic Ca++ and concurrent sensitivity to D600 was increased at lower concentrations of NE because the degree of Ca++ release and RLCa++E were relatively small. Additionally, it appears that RLCA++E may be attenuated by concomitant membrane depolarization.

Volume 247, Issue 1, pp. 223-234, 10/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics