Premium
Modulation of L‐type Ca 2+ Channels by β 3 ‐Adrenoceptor Activation and the Involvement of Nitric Oxide
Author(s) -
Au Alice L.S.,
Kwan Yiu Wa
Publication year - 2001
Publication title -
journal of cardiac surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.428
H-Index - 58
eISSN - 1540-8191
pISSN - 0886-0440
DOI - 10.1111/j.1540-8191.2001.tb01179.x
Subject(s) - nadolol , isoprenaline , medicine , endocrinology , nitric oxide , agonist , nitric oxide synthase , stimulation , receptor , propranolol
A bstract Background : Both β 1 ‐and β 2 ‐adrenoceptors (AR) in cardiac tissues are responsible for the excitatory effect of catecholamines. Recent evidence demonstrated the presence of another subtype ofβ‐AR (β 3 ‐AR) in cardiac ventricular preparation. Activation of β 3 ‐AR elicited a depressant response on ventricular contraction. The underlying mechanism(s) for the negative inotropism is relatively unknown. Methods : We investigated the effects of β 3 ‐AR activation on basal voltage‐dependent Ca 2+ channel (l CaL ) amplitude of the guinea pig enzyme‐dissociated single ventricular myocytes using amphotericin B (200 μg/mL) perforated‐patch whole‐cell patch‐clamp techniques (˜ 22°C). Results : Application of (‐)‐isoprenaline ((‐)‐ISO) (100 nM, a nonselective β‐AR agonist) increased the basal l CaL amplitude (˜ 210% of control) (n = 8). However, in the presence of nadolol (1 μM, a β 1 ‐/β 2 ‐AR antagonist), the stimulatory effect of (‐)‐ISO on l CaL was abolished and a slowly developed inhibition of the basal l CaL was recorded (˜ 80% of control) (n = 9). A smaller degree of inhibition was observed with BRL 37344 (100 nM, a selective β 3 ‐AR agonist) (58% of control) (n # 7). The inhibitory effect of (‐)‐ISO (with nadolol) and BRL 37344 persisted after washout. Pretreating the ventricular myocytes with L‐NAME (0.3 μM, a nitric oxide synthase inhibitor), but not D‐NAME (0.3 μM), abolished the inhibitory effect of (‐)‐ISO and BRL 37344 (n = 7–9). Conclusions : The results suggest that β 3 ‐ARs are present in ventricular myocytes. Activation of the β 3 ‐AR resulted in an inhibition of the basal l CaL amplitude probably due to the formation of nitric oxide.