Specific Uncoupling of Excitation and Contraction in Mammalian Cardiac Tissue by Lanthanum

Arterially cannulated rabbit interventricular septal tissue was exposed to 5-40 microM La in 2.5 mM Ca perfusate. Immediately following perfusion with La two concurrent events were consistently observed: (a) a rapid decline of active tension to a lesser steady-state value, and (b) an abrupt, release of short duration of tissue-bound Ca. The magnitude of both events was directly related to the [La](o). If the duration of exposure to La was brief, contractility returned toward normal upon return to the La-free perfusate. Elevation of [Ca](o) during exposure to La counteracted its effect and induced a concurrent displacement of tissue-bound La. Cellular action potentials recorded during brief perfusion with La demonstrated that essentially normal regenerative depolarization was maintained. Analysis of the quantities of (45)Ca released following exposure to 10 microM La indicated that this La-susceptible Ca was being displaced from a homogeneous pool-the one previously shown by Langer to represent contractile dependent Ca. These data led to the following conclusions: During perfusion with 2.5 mM Ca contractile dependent Ca was derived primarily from "superficially" located sites. La effected the release of contractile dependent Ca by modifying the normal permselectivity of this "superficial" membrane for activator Ca. These and other data infer that contractile dependent Ca is derived primarily from superficially located sites.