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Autonomic Receptors of the Early Rat Embryo Heart: Growth and Development 1

The adult heart rate responds to stimulation of the sympathetic and parasympathetic nervous system. These responses are mediated by the release of norepinephrine and acetylcholine (ACh) which act on beta-adre-nergic and on muscarinic-cholinergic receptors, respectively. During rat embryogene-sis, the heart commences to beat during Day 10 and circulation is established before these nerves reach and innervate the heart on Day 15 (1-3). The effect of ACh on the beat rate of excised rat embryo hearts has been reported by two groups of workers and their conclusions differed; Hall (4) observed a decrease in rate in the Day 11 ½ and older embryos but Pager et al. (5) could not demonstrate this effect until Day 16½. Our studies using the whole explanted embryo suggest an explanation for this discrepancy. Cholinergic receptors can be experimentally distinguished into two types by (a) their response to atropine, which selectively blocks muscarinic receptors, and (b) to curare, which selectively blocks nicotinic receptors. The experiments reported in this paper demonstrate the presence of cholinergic receptors in the preinnervated intact embryonic heart, consistent with Hall's result in the excised heart, classify them as being of the muscarinic type and show that they are independent of the adrenergic receptors in their action and time of functional appearance. We have found (6) in the explanted whole embryo that the adrenergic response of the heart appears during Day 10 concom-mitant with the onset of heart function, a result similar to that of Hall's with excised hearts. Our findings indicate that cholinergic response first appears approximately ½ day later in development than the adrenergic response, a finding also first observed by Hall. Methods. Embryos were explanted at either Day 10 1/2 (10–15 somites) or Day 11 (21-26 somites) of gestation. The explantation procedure followed was as described in New (7), Shepard et al. (8), and Robkin et al. (9).