NS-1619 is a selective large conductance Ca2+-activated K+-channel activator. The stimulation of outward currents by NS 1619 at -10 mV was independent of the presence of Ca2+ in the bath or pipette solutions but was antagonized by either charybdotoxin (250 nM) or penitrem A (100 nM) in the bath solution. NS 1619 (3-100 mM) produced a concentration-dependent inhibition of spontaneous activity in rat portal vein characterized by a reduction in the amplitude and duration of the tension waves. NS 1619 activates the large conductance, Ca2+-sensitive channel, BKca and over the same concentration range it inhibits both KV and L-type Ca-channels[3]. NS-1619 induced concentration-dependent activation of BKCa channels with a calculated EC50 of 32 mM. The NS 1619-induced activity was dependent on the presence of free Ca2+ at the intracellular surface, but was not associated with a change in channel voltage sensitivity[4]. When cell membrane voltage was stepped to test potentials (-60 to +60 mV) from a holding potential of -10 mV, NS 1619 increased the outwardly rectifying K+ current in a concentration-dependent manner. NS 1619 reduced electrically stimulated contractile responses of rat vas deferens in a concentration-dependent manner. NS 1619 (10-100 mM) reduced the high K+-induced contractions in a noncompetitive manner[5]. Inhalation of a 12 µM and 100 µM NS1619 solution significantly reduced RV (right ventricular) pressure without affecting systemic arterial pressure. In PASMC's, NS1619 (100 µM) significantly attenuated PASMC proliferation by a pathway independent of AKT and ERK1/2 activation[6].
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