| dc.description | The mechanisms of adrenergic stimulation of oscillatory afterpotentials (OAP) and transient inward current (TI) and the ionic basis of TI were studied in isolated rabbit cardiac Purkinje fibres with standard intracellular microelectrode recording and two-electrode voltage clamp techniques. Under non voltage clamp, specific $\alpha\sb1$-adrenergic stimulation increased the amplitude of OAP and induced triggered activity when sub-threshold OAP were induced by high Ca$\sp{2+}$. In contrast, specific $\alpha\sb1$-adrenergic stimulation decreased the amplitude of OAP and suppressed triggered activity induced by digitalis. $\alpha\sb1$-adrenergic stimulation had no effect on OAP and triggered activity. Thus, specific $\alpha\sb1$-adrenergic stimulation may exert either proarrhythmic or antiarrhythmic effects on OAP and triggered activity depending on the method of induction of OAP. Under voltage clamp, TI could be induced routinely by elevation of (Ca$\sp{2+}\rbrack\sb{\rm o}$ in the absence of (Na$\sp+\rbrack\sb{\rm o}$. High (Ca$\sp{2+}\rbrack\sb{\rm o}$ induced TI had a distinct reversal potential (E$\sb{\rm REV}$) either in the absence or in the presence of (Na$\sp+\rbrack\sb{\rm o}$. This suggests that TI is conducted through TI channels, not Na$\sp+$-Ca$\sp{2+}$ exchange. Further results suggest that Cl$\sp-$ contributes to generation of TI. Therefore, TI channel conductances are both cationic and anionic, and can be differentially modulated. $\beta$-adrenoceptor stimulation itself failed to induce the TI, but significantly increased peak magnitude of spontaneously occurring TI or TI induced by digitalis. The enhancement of TI seemed to be independent of the calcium current (I$\sb{\rm Ca}$) because agents known to block I$\sb{\rm Ca}$ failed to block this stimulation. When TI was induced by elevation of (Ca$\sp{2+}\rbrack\sb{\rm o}$, $\beta$-adrenergic stimulation had no effect on both inward and outward TI in the absence of (Na$\sp+\rbrack\sb{\rm o}$, but significantly increased both inward and outward TI in the presenceof (Na$\sp+\rbrack\sb{\rm o}$. This suggests that (Na$\sp+\rbrack\sb{\rm o}$ is essential in mediating $\beta$-adrenergic stimulation of TI. The stimulatory effects were abolished if preparations were previously treated with $\beta$-adrenoceptor blockers. However, once the enhancement of TI became apparent, $\beta$-adrenoceptor blocker only incompletely reversed the stimulation. Forskolin, a direct adenylate cyclase activator, strongly increased both inward and outward TI. However, these effects were absent in 0 (Na$\sp+\rbrack\sb{\rm o}$, $\beta$-adrenergic stimulation of either digitalis or high Ca$\sp{2+}$ induced TI could be blocked by putative Na$\sp+$-Ca$\sp{2+}$ exchanger blockers. Thus, $\beta$-adrenergic stimulation of TI seems to be mediated by cAMP-dependent phosphorylation of the Na$\sp+$-Ca$\sp{2+}$ exchanger protein which increases Ca$\sp{2+}$ loading of the cells. (Abstract shortened by UMI.) | en_US |
