COMPARISON BETA2 VS BETA1 ADRENOCEPTOR STIMULATION IN RAT CARDIOCYTE STIMULATION

点击翻译按钮获取中文摘要

Bolus beta1 and beta2 adrenoceptors exist in the heart. While the cellular effects of the former are widely studied, the specific effects of the later have not been elucidated. We studied the effects of beta2- and beta1-adrenoceptor (beta2AR and beta1AR) agonists on the cytosolic Ca2+ (Cai) transient, indexed by the transient increase in Indo-1 fluorescence ratio following excitation, twitch amplitude, measured via photodiode array, and membrane potential and L-type sarcolemmal Ca2+ current, and ICa, measured by whole cell patch electrode in single rat ventricular myocytes. The selective beta2AR agonist Zinterol (Zint) increased the amplitudes of both the Cai transient and twitch in a concentration- dependent manner. Similar results were obtained when beta2AR's were stimulated with isoproterenol (ISO) in the presence of the selective beta1AR antagonist, CGP 20712A (CGP). Beta1AR stimulation induced by norepinephrine (NE) increased twitch amplitude to about the same extent as beta2AR. However, several striking differences between response to beta1AR and beta2AR stimulation were observed. Beta1AR stimulation had a potent effect to abbreviate the time course of the twitch contraction and Cai transient; beta2AR stimulation did not reduce the time course of the Cai transient and had only a minor effect on the twitch duration. For a given increase in twitch amplitude, beta1AR stimulation caused a greater increase in Cai transient, suggesting a diminished Cai-myofilament interaction. beta1AR, but not beta2AR stimulation, evoked spontaneous Cai oscillations, increased the diastolic indo-fluorescence level and caused a decline in resting cell length. Beta1AR and beta2AR also differed in their effects on ICa. While both beta1AR and beta2AR stimulation increased the peak ICa amplitude, beta2 markedly prolonged the ICa inactivation time. Accordingly, beta2AR stimulation prolonged the action potential duration to a greater extent than beta1AR stimulation did. CPT cAMP mimicked the effects of beta1AR stimulation by NE but not those due to beta2AR stimulation. These results clearly indicate that both beta2AR and beta1AR adrenoceptors functionally coexist in rat ventricular myocytes, but that stimulation of these receptor subtypes elicits qualitatively different cell responses at the levels of ionic channels, the myofilaments, and sarcoplasmic reticulum (SR).