beta-Adrenergic relaxation of mouse urinary bladder smooth muscle in the absence of large-conductance Ca~(2+)-activated K+ channel

摘要

During the bladder filling phase, UBSM accommodates for increasing volumes of urine, providing adequate, low-pressure bladder storage capacity. A population of three different subtypes (P1-P3) of (3-adrenergic receptors ((3-ARs) mediates the UBSM relaxation in response to norepinephrine released from the sympathetic nerves (1). This sustained (3-adrenergic UBSM relaxation facilitates the urine storage by increasing the capacity of the bladder during its filling phase. In UBSM, (3-ARs mediate their effect using cAMP as a second messenger and the cAMP-dependent protein kinase (PKA) (for reviews, see Refs. 1 and 25). In guinea pig UBSM, isoproterenol, a nonselective (3-AR agonist, inhibits spontaneous action potentials with the associated Ca~(2+) transients and hyperpolarizes the membrane through PKA activation to mediate relaxation (16). In addition, BK channels can be activated by isoproterenol or by forskolin, an adenylyl cyclase activator that increases intracellular cAMP levels and PKA activity (12), suggesting they play a role in (3-AR-mediated relaxation. Using the patch-clamp technique, we have further shown that in guinea pig, UBSM stimulation of (3-ARs with isoproterenol activates the BK channels via modulation of localized intracellular Ca~(2+) signals, known as "Ca~(2+) sparks," and by increasing the Ca~(2+) influx via L-type Ca_v channels (20).