Vol. 301, Issue 3, 893-899, June 2002

Differential Rate Responses to Nicotine in Rat Heart: Evidence for Two Classes of Nicotinic Receptors

Susan Ji, Toshimasa Tosaka, Bernard H. Whitfield, Alexander N. Katchman, Abdurrahman Kandil, Bjoern C. Knollmann and Steven N. Ebert

Department of Pharmacology, Georgetown University Medical Center, Washington, DC

Nicotinic acetylcholine receptors are pentameric, typically being composed of two or more different subunits. To investigate which receptor subtypes are active in the heart, we initiated a series of experiments using an isolated perfused rat heart (Langendorff) preparation. Nicotine administration (100 µM) caused a brief decrease (7 ± 2%) followed by a much larger increase (17 ± 5%) in heart rate that slowly returned to baseline within 10 to 15 min. The nicotine-induced decrease in heart rate could be abolished by an 7-specific antagonist, -bungarotoxin (100 nM). In contrast, the nicotine-induced increase in heart rate persisted in the presence of -bungarotoxin. These results suggest that the nicotinic acetylcholine receptors (nAChRs) that mediate the initial decrease in heart rate probably contain 7 subunits, whereas those that mediate the increase in heart rate probably do not contain 7 subunits. To investigate which subunits may contribute to the nicotine-induced increase in heart rate, we repeated our experiments with cytisine, an agonist at nAChRs that contain 4 subunits. The cytisine results were similar to those obtained with nicotine, thereby suggesting that the nAChRs on sympathetic nerve terminals in the heart probably contain 4 subunits. Thus, the results of this study show that pharmacologically distinct nAChRs are responsible for the differential effects of nicotine on heart rate. More specifically, our results suggest that 7 subunits participate in the initial nicotine-induced heart rate decrease, whereas 4 subunits help to mediate the subsequent nicotine-induced rise in heart rate.