Interactive α- and β-adrenergic actions of norepinephrine in rat cardiac myocytes

Abstract

We investigated the effects of the physiological neurotransmitter norepinephrine on the contractile properties and Ca 2+ dynamics of isolated cardiac myocytes, with particular emphasis on possible interactions between α- and β-adrenergic effects. Individual rat ventricular myocytes were electrically stimulated at a frequency of 1 Hz. Norepinephrine (10 −9 to 10 −5 m) increased extent and velocity of shortening and decreased the contraction duration. β-Adrenergic activation gave a greater enhancement of extent and velocity of shortening than did norepinephrine alone (i.e. α plus β). Neither α 1 nor α 2 adrenergic activation individually produced a significant impact upon contraction. Using suspensions of myocytes loaded with Quin-2, we also studied resting levels of cytosolic Ca 2+ ([Ca 2+] c), the increase of [Ca 2+] c due to caffeine-addition (as an index of sarcoplasmic reticulum Ca 2+ content) and the subsequent increase in [Ca 2+] c due to depolarization with 30 m m K + (as an index of sarcolemmal voltage-dependent Ca 2+ channel activity). Norepinephrine decreased resting [Ca 2+] c, increased sarcoplasmic reticulum Ca 2+ content and increased Ca 2+ channel activity. β-Adrenergic activation produced the same effect on resting [Ca 2+] c and sarcoplasmic reticulum content, but gave significantly greater activation of sarcolemmal Ca 2+ channel activity, than did norepinephrine (α plus β). By contrast, α-adrenergic stimulation had no effect on resting [Ca 2+] c or sarcoplasmic reticulum Ca 2+ content. We conclude that β-mediated effects predominate in the action of the physiological agonist norepinephrine on cardiac myocytes. However, α (specifically α 1)-adrenergic effects are significant in diminishing the potentiation of the extent and velocity of shortening, and of depolarization-induced entry of Ca 2+ into the cell, which is seen on β-stimulation alone. Thus, there may be an intrinsic feedback effect in the actions of norepinephrine on the cardiac myocyte.