Calcium Current Channels Induced by Catecholamines in Chick Embryonic Hearts Whose Fast Sodium Channels are Blocked by Tetrodotoxin or Elevated Potassium

Abstract

In isolated ventricles of old (9-19 day) chick embryonic hearts made inexcitable by inactivating the fast sodium channels with either tetrodotoxin (TTX) or elevated external potassium, catecholamines induced slow electrical responses and concomitant contractions within 1-3 minutes. These slow responses had a higher threshold and propagated at a slower velocity than did the normal action potential. They were often graded and quite variable from one region of the heart to another. They were blocked by lanthanum or manganese (1 mM) and showed a dependence on the external calcium level. Strontium and barium could substitute for calcium. The slow channels were not completely inactivated when the external potassium concentration was raised until low membrane potentials of -10 to -25 mv were reached. The catecholamine-induced responses had a shape similar to that of the plateau component of the normal action potential, and cooling affected both in a similar manner. In some cases, slow responses persisted in TTX-blocked hearts even without the addition of exogenous catecholamines. Cyclic 3',5' AMP, dibutyryl cyclic AMP, theophylline, and caffeine partially mimicked the catecholamines, but usually the development of the response to these drugs was much slower. Prostaglandins, ryanodine, and acetylcholine had no effect. The order of effectiveness of the catecholamines was isoproterenol > epinephrine ≥ norepinephrine > dopamine ≥ dopa. Phenylalanine and tyrosine were ineffective. Isoproterenol produced a near-maximal effect at 5 x 10^-7M. Propranolol blocked the catecholamine-induced effects. In young (2-5 day) hearts, there was no evidence that catecholamines produced a similar effect, and they did not have a positive inotropic action or an effect on the slow sodium channels. The results suggest that catecholamines quickly increase the density of divalent cation channels available in the sarcolemma of older chick hearts, thereby increasing the inward Ca^2- current and influencing contraction.