β₁-Adrenoceptor stimulation and β₂-adrenoceptor stimulation differ in their effects on contraction, cytosolic Ca²⁺, and Ca²⁺ current in single rat ventricular cells

The effects of β₂- and β₁-adrenoceptor (β₂AR and β₁AR, respectively) agonists on the cytosolic Ca²⁺ (Ca(i)) transient (indexed by the transient increase in indo-1 fluorescence ratio after excitation), twitch amplitude (measured via photodiode array), membrane potential, and L-type sarcolemmal Ca²⁺ current (I(Ca), measured by whole-cell patch electrode) were assessed in single rat ventricular myocytes. The selective β₂AR agonist Zinterol increased the amplitudes of both the Ca(i) transient and twitch in a concentration-dependent manner. Similar results were obtained when β₂ARs were stimulated with isoproterenol in the presence of the selective β₁AR antagonist CGP 20712A. β₁AR stimulation induced by norepinephrine increased twitch amplitude to about the same extent as did β₂AR stimulation. However, several striking differences between response to β₁AR and β₂AR stimulation were observed. β₁AR stimulation had the potent effect of abbreviating the time course of the contraction and Ca(i) transient, and β₂AR stimulation did not reduce the time course of the Ca(i) transient and had only a minor effect on the twitch duration. For a given increase in twitch amplitude, β₁AR stimulation caused a greater increase in Ca(i) transient, suggesting a diminished Ca(i)-myofilament interaction. β₁AR, but not β₂AR, stimulation evoked spontaneous Ca(i) oscillations, increased the diastolic indo fluorescence level, and caused a decline in resting cell length. β₁AR and β₂AR also differed in their effects on I(Ca). Whereas both β₁AR and β₂AR stimulation increased the peak I(Ca) amplitude, β₂AR stimulation markedly prolonged the I(Ca) inactivation time. Accordingly, β₂AR stimulation prolonged the action potential duration to a greater extent than did β₁AR stimulation. 8-(4-Chlorophenylthio)cAMP mimicked the effects of β₁AR stimulation by norepinephrine but not those due to β₂AR stimulation. These results clearly indicate that both β₂ARs and β₁ARs 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.