Evidence that action potential generation is not the exclusive determinant to trigger spontaneous myogenic contraction of guinea‐pig urinary bladder smooth muscle

Abstract

Urinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This spontaneous mechanical activity is myogenic and can be closely related to the UBSM cell action potential to facilitate Ca2+ influx through voltage-gated Ca2+ channels. In the present study, to know whether this membrane electrical event is the exclusive mechanism to trigger spontaneous smooth muscle contraction, we compared the inhibitory effects of Ca2+ channel blockers on the spontaneous action potential and mechanical activity in the isolated guinea-pig UBSM. Both action potential and rhythmic contraction were generated spontaneously in the presence of atropine (1 microM), phentolamine (1 microM), propranolol (1 microM), suramin (10 microM) and tetrodotoxin (1 microM), which suggest that both phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 microM) completely eliminated the generation of action potential whereas its frequency was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1 microM). In contrast to disappearance of action potential in the presence of Ca2+ channel blockers, spontaneous contraction of UBSM was inhibited only partly by nisoldipine or diltiazem and most of the mechanical components persisted in these channel blockers. These results indicate that spontaneous action potential in UBSM cell is generated through the activation of L-type voltage-gated Ca2+ channels. The subsequent elevation of intracellular Ca2+ concentrations during a burst of action potentials can be partly responsible for the induction of UBSM mechanical activity. In addition, the present study provides evidence that UBSM spontaneous mechanical activity is also attributable to the mechanism(s) other than the generation of Ca2+ spike.

Muscarinic regulation of neonatal rat bladder spontaneous contractions

“…Spontaneous contractions are always preceded by spontaneous action potentials (12,18), the upstroke of which is due to influx of Ca 2ϩ through the L-type channels (14). Blockade of L-type Ca 2ϩ channels with nifidepine abolished spontaneous action potentials and spontaneous contractions in normal bladders (12,14,15,18,20), whereas activation of L-type Ca 2ϩ channels with the dihydropyridine analog S-(Ϫ)-BAY K 8644 enhanced the amplitude and the frequency of spontaneous contractions in normal and diabetic adult rat bladder smooth muscle strips (5,26). We confirm that enhanced Ca 2ϩ influx by activation of L-type Ca 2ϩ channels alone was sufficient to increase the spontaneous contractions in 1-to 2-wk-old bladders.…”

Phospholipase C Inhibitors Suppress Spontaneous Mechanical Activity of Guinea Pig Urinary Bladder Smooth Muscle

“…[1][2][3] However, our previous findings show that most of the components of UBSM mechanical activity can be generated in the presence of nisoldipine or diltiazem, although these Ca 2ϩ channel inhibitors completely eliminate the generation of action potential. 3,8) This result implies that the action potential is not the exclusive triggering mechanism by which spontaneous contraction is induced in UBSM. 8) The possible existence of a pacemaker mechanism other than the action potential can also be supported by an apparent dissociation between membrane electrical events and mechanical activity in the presence of 2-aminoethoxydiphenyl borate (2-APB).…”

“…3,8) This result implies that the action potential is not the exclusive triggering mechanism by which spontaneous contraction is induced in UBSM. 8) The possible existence of a pacemaker mechanism other than the action potential can also be supported by an apparent dissociation between membrane electrical events and mechanical activity in the presence of 2-aminoethoxydiphenyl borate (2-APB). 9) The inositol 1,4,5-trisphosphate (IP 3 ) receptor-inhibitory property of this compound 10,11) leads to the assumption that the activation of phospholipase C (PLC) and subsequent IP 3 -induced Ca 2ϩ release system plays a role in inducing spontaneous mechanical activity of UBSM.…”

“…3,12) For intracellular recordings, a thin layer of muscle bundles (three to five bundles) was prepared (1-3 mm in widthϫ3-6 mm in length). 8,9) Measurement of Spontaneous Rhythmic Contraction of UBSM Spontaneous rhythmic contractions were recorded as reported previously. 3,8) Tension changes were isometrically recorded with a force-displacement transducer (TB-612T, Nihon-Kohden, Tokyo, Japan) connected to a minipolygraph (Signal Conditioner: Model MSC-2, Labo Support, Co., Ltd., Osaka, Japan).…”

“…8,9) Measurement of Spontaneous Rhythmic Contraction of UBSM Spontaneous rhythmic contractions were recorded as reported previously. 3,8) Tension changes were isometrically recorded with a force-displacement transducer (TB-612T, Nihon-Kohden, Tokyo, Japan) connected to a minipolygraph (Signal Conditioner: Model MSC-2, Labo Support, Co., Ltd., Osaka, Japan). Data were collected with MacLab/400 TM and Chart TM (Version 3.5.6) software (ADInstruments Japan, Tokyo, Japan).…”