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- Hougaard, C. et al. (2009) J. Pharmacol. Exp. Ther. 328, 28.
- Alomone Labs NS-4591 activates KCa3.1 currents expressed in HEK 293T cells.A. Time course of KCa3.1 current amplitude and its activation by 1 µM NS-4591 (#N-325). Currents were elicited by application of voltage ramp from -120 mV to +60 mV (150 msec), delivered every 10 seconds, holding potential of -80mV. B. Superimposed example traces of current responses before and during perfusion of 1 µM NS-4591 as indicated.
- Wei, A.D. et al. (2005) Pharmacol. Rev. 57, 463.
- Hougaard, C. et al. (2009) J. Pharmacol. Exp. Ther. 328, 28.
Calcium activated potassium (KCa) channels include three types of small-conductance channels, KCa2.1, KCa2.2 and KCa2.3, and the intermediate conductance channel KCa3.1. Both small- and intermediate-conductance KCa channels play important roles in many processes involving Ca2+-dependent signaling in both electrically excitable and non-excitable cells1.
NS-4591 is a potent synthetic activator of KCa3.1 and KCa2 channels. It has an effective concentration of 0.01-5 μM. NS-4591 does not seem to affect KCa1.1 or NaV channels but does cause a small reduction in CaV currents and a prominent reduction in delayed rectifier KV channel. In whole-cell patch-clamp experiments conducted, NS-4591 doubled IK-mediated currents at a concentration of 45±6 nM while 530±100 nM was required for doubling of SK3-mediated currents. The effect of NS-4591 was also examined in acutely dissociated bladder primary afferent neurons and NS-4591 was shown to inhibit the number of action potentials generated by suprathreshold depolarizing pulses. NS-4591 reduces the amplitude of detrusor twitches in a concentration dependent manner. in vivo experiments in rats and cats have demonstrated that 30 mg/kg inhibits bladder hyper activity induced by capsaicin and acetic acid. NS-4591 might prove to be an important agent for the treatment of bladder hyperactivity.
NS-4591 (#N-325) is a highly pure, synthetic, and biologically active compound.
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