Calcium activated potassium (K_Ca) channels include three types of small-conductance channels, K_Ca2.1, K_Ca2.2 and K_Ca2.3, and the intermediate conductance channel K_Ca3.1. Both small- and intermediate-conductance K_Ca 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 K_Ca3.1 and K_Ca2 channels. It has an effective concentration of 0.01-5 μM. NS-4591 does not seem to affect K_Ca1.1 or Na_V channels but does cause a small reduction in Ca_V currents and a prominent reduction in delayed rectifier K_V channel. In whole-cell patch-clamp experiments conducted, NS-4591 doubled I_K-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.