The elevation of protein kinase A (PKA) activity activates the large-conductance voltage- and @entity141 -activated K(+) (BK) channels in urinary bladder smooth muscle (UBSM) cells and consequently attenuates spontaneous phasic contractions of UBSM. However, the role of constitutive PKA activity in UBSM function has not been studied. Here, we tested the hypothesis that constitutive PKA activity is essential for controlling the excitability and contractility of UBSM. We used patch clamp electrophysiology, line-scanning confocal and ratiometric fluorescence microscopy on freshly isolated @entity840 UBSM cells, and isometric tension recordings on freshly isolated UBSM strips. Pharmacological inhibition of the constitutive PKA activity with @entity9501 or PKI 14-22 significantly reduced the frequency and amplitude of spontaneous transient BK channel currents (TBKCs) in UBSM cells. Confocal and ratiometric fluorescence microscopy studies revealed that inhibition of constitutive PKA activity with @entity9501 reduced the frequency and amplitude of the localized @entity141 sparks but increased global @entity141 levels and the magnitude of @entity141 oscillations in UBSM cells. @entity9501 abolished the spontaneous transient membrane hyperpolarizations and depolarized the membrane potential in UBSM cells. Inhibition of PKA with @entity9501 or @entity12176 also increased the amplitude and muscle force of UBSM spontaneous phasic contractions. This study reveals the novel concept that constitutive PKA activity is essential for controlling localized @entity141 signals generated by intracellular @entity141 stores and cytosolic @entity141 levels. Furthermore, constitutive PKA activity is critical for mediating the spontaneous TBKCs in UBSM cells, where it plays a key role in regulating spontaneous phasic contractions in UBSM.

Constitutive PKA activity is essential for maintaining the excitability and contractility in XXXX urinary bladder smooth muscle: role of the BK channel.

@entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity840 :: ('10141', 'Species') :: ['guinea pig'] @entity9501 :: ('MESH:C063509', 'Chemical') :: ['H-89'] @entity12176 :: ('MESH:C057416', 'Chemical') :: ['KT-5720']
@entity840 :: (10141,Species) :: ['guinea pig']
