K7 Channel Pharmacological Activation by the Novel Activator ML213: Role for Heteromeric K7.4/K7.5 Channels in Guinea Pig Detrusor Smooth Muscle Function.

Voltage-gated K7 channels (K7.1 to K7.5) are important regulators of the cell membrane potential in detrusor smooth muscle (DSM) of the urinary bladder.

Nongenomic modulation of the large conductance voltage- and Ca-activated K channels by estrogen: A novel regulatory mechanism in human detrusor smooth muscle.

Estrogens have an important role in regulating detrusor smooth muscle (DSM) function. However, the underlying molecular and cellular mechanisms by which estrogens control human DSM excitability and contractility are not well known. Here, we used human DSM specimens from open bladder surgeries on 27 patients to elucidate the mechanism by which 17-estradiol regulates large conductance voltage- and Ca-activated K (BK) channels, the most prominent K channels in human DSM We employed single BK channel recordings on inside-out excised membrane patches, perforated whole-cell patch-clamp on freshly isolated DSM cells, and isometric tension recordings on DSM-isolated strips to investigate the mechanism by which 17-estradiol activates BK channels.

Regulation of transient receptor potential melastatin 4 channel by sarcoplasmic reticulum inositol trisphosphate receptors: Role in human detrusor smooth muscle function.

We recently reported key physiologic roles for Ca-activated transient receptor potential melastatin 4 (TRPM4) channels in detrusor smooth muscle (DSM). However, the Ca-signaling mechanisms governing TRPM4 channel activity in human DSM cells are unexplored. As the TRPM4 channels are activated by Ca, inositol 1,4,5-trisphosphate receptor (IPR)-mediated Ca release from the sarcoplasmic reticulum represents a potential Ca source for TRPM4 channel activation.

Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels.

In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability.

Regulation of Guinea Pig Detrusor Smooth Muscle Excitability by 17β-Estradiol: The Role of the Large Conductance Voltage- and Ca2+-Activated K+ Channels.

Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens.

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility.

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1-KV7.5) in detrusor smooth muscle (DSM) are poorly understood.

Prostaglandin E2 excitatory effects on guinea pig urinary bladder smooth muscle: a novel regulatory mechanism mediated by large-conductance voltage- and Ca2+-activated K+ channels.

Prostaglandin E2 (PGE2) is an essential signaling molecule involved in the regulation of detrusor smooth muscle (DSM) function. However, the underlying regulatory mechanism by which PGE2 augments DSM cell excitability and contractility is not well understood. Here, we investigated whether PGE2 inhibits the large conductance voltage- and Ca(2+)-activated K(+) (BK) channels in guinea pig DSM, thereby increasing DSM excitability and contractility.

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels.

Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca(2+)-activated K(+) (BK) channels or L-type voltage-dependent Ca(2+) channels (VDCCs), major regulators of DSM excitability and contractility, are targets for EtOH by patch-clamp electrophysiology (conventional and perforated whole cell and excised patch single channel) and isometric tension recordings using guinea pig DSM cells and isolated tissue strips, respectively. EtOH at 0.