ISSN:
1432-1912
Keywords:
BMS-180448
;
Cardiac muscle
;
Smooth muscle
;
Electrophysiology
;
86Rb fluxes
;
Potassium channel activators
;
Glyburide Alinidine
;
Alinidine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The goal of the present study was to further characterize the effects of the novel cardioprotective agent BMS-180448 on potassium fluxes in cardiac and vascular smooth muscle. Exposure of voltage-clamped guinea pig ventricular myocytes to BMS-180448 (300 μM) produced an inhibition of IK followed by the delayed (5.5 ± 0.5 min) activation of a large time-independent potassium current. At 100 μM, BMS-180448 produced only inhibition of IK. The BMS-180448 activated current was refractory to block by 30 μM, glyburide but was largely inhibited by 100 μM alinidine (84 ± 6% inhibition at + 40 mV). Cromakalim (100 μM)-activated currents were fully inhibited by 3 μM, glyburide and 79 ± 4% blocked by 100 μM alinidine. The current responses to BMS-180448 were unaffected by the inclusion of 10 mM UDP (100 μM, ATP) in the pipette. BMS-180448 also produced a concentrationdependent increase in 86Rb efflux from aortic strips; efflux responses were increased in low calcium medium and fully antagonized by 3 μM, glyburide. Thus, BMS-180448 activates a potassium conductance in both cardiac and smooth muscle. The glyburide sensitivity of the BMS-180448-induced increase in 86Rb efflux from the aortic preparations suggests that this drug activates IKATP in vascular smooth muscle. Moreover, the observation that BMS-180448 (100 μM) partially inhibits the effects of cromakalim in ventricular muscle cells suggests that these drugs interact, directly or indirectly, with a common site in cardiac muscle.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00168435
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