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.
- Ca current
- Ca transient
- cardiac cells
- β-adrenergic receptor subtypes
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine