Modulation of L-type Ca2+ channels by beta(3)-adrenoceptor activation and the involvement of nitric oxide
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AbstractBackground. Both beta(1)- and beta(2)-adrenoceptors (AR) in cardiac tissues are responsible for the excitatory effect of catecholamines. Recent evidence demonstrated the presence of another subtype of beta-AR (beta(3)-AR) in cardiac ventricular preparation. Activation of beta(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 beta(3)-AR activation on basal voltage-dependent Ca2+ channel (I-CaL amplitude of the guinea pig enzyme-dissociated single ventricular myocytes using amphotericin B (200 mug/mL) perforated-patch whole-cell patch-clamp techniques (similar to 22degreesC). Results: Application of (-)-isoprenaline ((-)-ISO) (100 nM, a nonselective beta-AR agonist) increased the basal I-CaL amplitude (similar to 210% of control) (n = 8). However, in the presence of nadolol (1 muM, a beta(1)-/beta(2)-AR antagonist), the stimulatory effect of (-)-ISO on I-CaL was abolished and a slowly developed inhibition of the basal I-CaL was recorded (similar to 80% of control) (n = 9). A smaller degree of inhibition was observed with BRL 37344 (100 nM, a selective beta(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 10.3 muM, a nitric oxide synthase inhibitor), but not D-NAME (0.3 muM), abolished the inhibitory effect of (-)-ISO and BRL 37344 (n = 7-9). Conclusions: The results suggest that beta(3)-ARs are present in ventricular myocytes. Activation of the beta(3)-AR resulted in an inhibition of the basal I-CaL amplitude probably due to the formation of nitric oxide.
All Author(s) ListAu ALS, Kwan YW
Name of Conference1st International Symposium on Cardiovascular Science
Start Date of Conference23/11/2001
End Date of Conference24/11/2001
Place of ConferenceHONG KONG
Journal nameJournal of Cardiac Surgery
Volume Number17
Issue Number5
Pages465 - 469
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesCardiac & Cardiovascular Systems; CARDIAC & CARDIOVASCULAR SYSTEMS; Cardiovascular System & Cardiology; Surgery; SURGERY

Last updated on 2020-21-10 at 00:33