Interactive alpha- and beta-adrenergic actions of norepinephrine in rat cardiac myocytes.

We investigated the effects of the physiological neurotransmitter norepinephrine on the contractile properties and Ca2+ dynamics of isolated cardiac myocytes, with particular emphasis on possible interactions between alpha- and beta-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. beta-Adrenergic activation gave a greater enhancement of extent and velocity of shortening than did norepinephrine alone (i.e. alpha plus beta). Neither alpha 1 nor alpha 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 Ca2+ ([ Ca2+]c), the increase of [Ca2+]c due to caffeine-addition (as an index of sarcoplasmic reticulum Ca2+ content) and the subsequent increase in [Ca2+]c due to depolarization with 30 mM K+ (as an index of sarcolemmal voltage-dependent Ca2+ channel activity). Norepinephrine decreased resting [Ca2+]c, increased sarcoplasmic reticulum Ca2+ content and increased Ca2+ channel activity. beta-Adrenergic activation produced the same effect on resting [Ca2+]c and sarcoplasmic reticulum content, but gave significantly greater activation of sarcolemmal Ca2+ channel activity, than did norepinephrine (alpha plus beta). By contrast, alpha-adrenergic stimulation had no effect on resting [Ca2+]c or sarcoplasmic reticulum Ca2+ content. We conclude that beta-mediated effects predominate in the action of the physiological agonist norepinephrine on cardiac myocytes. However, alpha (specifically alpha 1)-adrenergic effects are significant in diminishing the potentiation of the extent and velocity of shortening, and of depolarization-induced entry of Ca2+ into the cell, which is seen on beta-stimulation alone. Thus, there may be an intrinsic feedback effect in the actions of norepinephrine on the cardiac myocyte.