Bladder hyperpolarization

During the action potential in vas deferens or urinary bladder the rise in [Ca2+] close under the cell membrane is responsible, in combination with the depolarization, for the repolarization phase as it causes the opening of Ca2+-activated K+ channels through which a large repolarizing outward current flows (Arnaudeau et al 1997, Imaizumi et al 1998, Ohi et al 2001). This may lead to a transient period of hyperpolarization (an afterhyperpolarization ) following the action potential (Imaizumi et al 1998). 

A structurally novel series of substituted 10//-benzo[4,5]furo[3,2- ]indole-l-carboxylic acids 504-507 was prepared and shown to possess potent, bladder-selective smooth muscle relaxant properties and thus is potentially useful for the treatment of urge urinary incontinence. Electrophysiological studies using rat detrusor myocytes have demonstrated that prototype compound 8 produces a significant increase in hyperpolarizing current, which is iberiotoxin (IbTx)-reversed, thus consistent with activation of the large-conductance Ca -activated potassium channel (BKca) <2001BML2093>. 

---