Role Of Ca2+-Activated K+ Channel in the Neurogenic Contractions Induced by Electrical Field Stimulation in Detrusor Smooth Muscle Isolated from Rats and Guinea Pigs

Abstract

Our previous studies revealed a key role for the Ca2+-activated K+ (BK) channel in determining the spontaneous contractions of detrusor smooth muscle (DSM) in mammals. Using tissue baths and isometric smooth muscle tension recordings, we examined the contribution of BK channels in the neurogenic contractions of DSM strips isolated from rats and Guinea pigs. Neurogenic contractions were induced by increasing electrical field stimulation (EFS) frequencies (0.5-50 Hz) under stimuli with constant amplitude (20 V), pulse width (0.75 ms), and duration (3 s). These EFS-induced contractions were abolished by the Na+ channel inhibitor, tetrodotoxin (1 ∈1/4M), indicating their neurogenic origin. Blocking the BK channel with its specific inhibitor, iberiotoxin (200 nM), caused a statistically significant increase in the EFS-induced contraction amplitude at all stimulation frequencies in both species. We further dissected the BK channel contribution to the cholinergic and purinergic neurogenic contractions using specific neurotransmitter receptor inhibitors. Atropine (1 ∈1/4M) was used to block the cholinergic component and a combination of suramin (10 ∈1/4M), and α,β-meth-ATP (10 ∈1/4M), was used to block the purinergic component of the EFS-induced neurogenic contractions. In both species, blocking the BK channel caused a statistically significant increase in both cholinergic and purinergic components of the EFS-induced neurogenic contraction amplitude. However, the BK channel contributed more to the purinergic component. With a blocked BK channel, the maximum response of the purinergic component was doubled and achieved at lower frequencies of stimulation. Time controls were performed for each experimental series to confirm the stability of the preparations. The data indicate that the BK channels function to oppose neurogenic contractions in rat and Guinea pig DSM. Supported by NIH DK084284 & DK070909.