Developmental changes in β‐adrenergic and cholinergic interactions on calcium‐dependent slow action potentials in rat ventricular muscles

Abstract

1 Developmental changes in the effect of isoprenaline (Iso) and acetylcholine (ACh) interactions on Ca2"-dependent slow action potentials (APs) were studied in the ventricular muscles of foetal (12-20 days post-gestation), neonatal (0-20 days old), and adult (2-3 months old) rats. The slow APs were recorded at 0.2 Hz in partially depolarized preparations (an extracellular K + concentration of 25 mM).2 Iso (1 nm to IO yM) began to increase the Vn x of the slow APs (an approximate indicator of Ca2+ current) on foetal day 18; its potentiating effect became greater with age and reached the adult level about 2 weeks after birth.3 ACh (10pM) abolished the Iso (1 pM)-induced increased in the V.. observed in the late foetal and neonatal periods.4 The inhibitory effect of ACh on the Pmax was antagonized by atropine but not by pirenzepine, suggesting that ACh reduces Ca2 + current (in the presence of ,B-adrenoceptor agonists) by stimulating muscarinic (M2) cholinoceptors. 5 These results suggest that developmental changes in the modulatory effects of f-adrenoceptor and cholinoceptor agonists on Ca2+ channels occur from a few days before birth to 2 weeks after birth and that the functional coupling between muscarinic cholinoceptors and Ca2 + channels has already been established when the coupling between P-adrenoceptors and Ca2 + channels starts to operate.

Developmental changes in β‐adrenoceptors, muscarinic cholinoceptors and Ca2+ channels in rat ventricular muscles

“…Our data are essentially similar to those of Kazazoglou et al (1983). These discrepancies between the B, data expressed in different units may be due largely to the following: (i) the ratio of 'mg protein/mg tissue' increases with age, i.e., 0.055 + 0.005 (n = 6) on day 16 post-gestation, 0.076 ± 0.003 (n = 13) on the day of birth, 0.111 + 0.004 (n = 12) on neonatal day 10, 0.123 + 0.006 (n = 11) on neonatal day 20, and 0.144 + 0.006 (n = 12) at adult ages of 2-3 months (the present data); (ii) the ratio of 'sarcolemmal protein/cell protein' or 'surface area/ fibre mass' decreases with age because of the development of intracellular organs (Baker & Potter, 1980;Whitsett & Darovec-Beckerman, 1981;Nedoma et al, 1986 (Kojima et al, 1988) are more similar to those of Iso-induced increases in Px (Kojima et al, 1990) (Kojima et al, 1990). This developmental time course correlates well with that of Ca2+ channels (present data) and of stimulatory GTP-binding (G,) proteins (Kojima et al, 1988).…”

“…The 'fmol mg 1 protein' unit is most commonly used, but sometimes it is the 'fmol mg'-tissue' unit. The biochemical findings previously reported, therefore, cannot adequately explain our previous electrophysiological data on the developmental Macmillan Press Ltd, 1990 ONTOGENY OF #-RECEPTORS, MUSCARINIC RECEPTORS & Ca2+ CHANNELS Yamamura & Snyder (1974), and Erman et al (1983) (Kojima et al, 1990).…”

“…The method of obtaining foetuses and neonates of specified ages has been described (Kojima et al, 1990 …”

“…The number of P-adrenoceptors, however, reached its peak about one week earlier than did the other three parameters (Figure 7). T1 6 Acetylcholine (ACh) almost completely abolished the Isoinduced increase in V,, observed on post-gestation days 18-20 and neonatal days 0-20 as well as in adult rats (Kojima et al, 1990). This finding can be explained by the following facts: (i) the density of muscarinic cholinoceptors is higher than that of fi-adrenoceptors and of Ca2 + channels during the developmental period examined, and (ii) the number of muscarinic cholinoceptors reaches a peak 1-2 weeks earlier than does that of fJ-adrenoceptors, of Ca2+ channels (present data) and of G, protein levels (Kojima et al, 1988).…”

“…The main findings from our previous study (Kojima et al, 1990) were: (i) isoprenaline (Iso) increased V,,., [the maximum rate of rise of action potential (AP)] of slow APs from post-gestation day 18, and its increasing effect reached the adult level about 2 weeks after birth; (ii) acetylcholine (ACh) became effective on post-gestation day 18 in reducing the P,,.X of Iso-induced slow APs to the level before the administration of Iso, and its inhibitory effect became greater as the ',,,,,x of Iso-induced slow APs increased with age. As described previously (Kojima et al, 1990), the transmembrane signalling mechanism following stimulation of f-adrenoceptors and muscarinic cholinoceptors by their agon- ' Author for correspondence.…”