Dependency of detrusor contractions on calcium sensitization and calcium entry through LOE‐908‐sensitive channels

Abstract

1 The subcellular mechanisms regulating stimulus-contraction coupling in detrusor remain to be determined. We used Ca

2-Aminoethoxydiphenyl borate (2-APB) antagonises inositol 1,4,5-trisphosphate-induced calcium release, inhibits calcium pumps and has a use-dependent and slowly reversible action on store-operated calcium entry channels

“…donate (data not shown), consistent with observations using HEK-293 cells [32]. Several other non-voltage-activated Ca 2+ entry pathways that are distinct from SOC are also not inhibited by 2-APB, including maitotoxin-evoked Ca 2+ entry in hepatocytes [17], S-nitrosylation-induced influx in a smooth muscle cell line [33], Ca 2+ influx caused by diacylglycerol analogues in PC12 cells [34], muscarinic activation of non-selective cation channels in smooth muscle [35]. In many instances, 2-APB can be used to block SOC-mediated Ca 2+ influx, although it should be noted that it is not completely specific for SOC [10].…”

Evidence that actomyosin cross bridges contribute to “passive” tension in detrusor smooth muscle

“…The dependency of resting striated muscle stiffness on Ca 2ϩ is one reason that a portion of resting tension is attributed to cross bridges. In the present and previous studies (1, 46 -48), APS and the resulting passive tension in DSM are generated by contracting muscle strips at L s with KCl, carbachol, or PGE 2 in a Ca 2ϩ -containing solution, but then measured in tissues incubated for at least 2-5 min in a Ca 2ϩ -free solution, a duration sufficient to abolish a KClinduced contraction (22). An early study indicated that smooth muscle displays a resistance to stretch when tissues are bathed in a Ca 2ϩ -containing medium that is absent when tissues are bathed in a Ca 2ϩ -free solution (42).…”

“…To induce active contraction, tissues were stimulated by addition of KCl (PSS in which 110 mM KCl was substituted iso-osmotically for NaCl). Strips of rabbit DSM contract strongly to KCl in the presence of Ca 2ϩ , but incubation for only 2 min in a Ca 2ϩ -free solution prevents KCl from causing a contraction (22).…”

“…This stiffness component is considered "passive" because tissues were bathed in a Ca 2ϩ -free solution ( Fig. 2A, Ca 2ϩ -free) that abolishes the ability of KCl to cause contraction (22).…”

Two Types of Cation Channel Activated by Stimulation of Muscarinic Receptors in Guinea-Pig Urinary Bladder Smooth Muscle

“…15). In the urinary bladder, however, no direct evidence has been provided for cation channel activation by muscarinic receptor stimulation; although there have been some positive results from analysis of contractions, the contractile responses produced by muscarinic receptor stimulation were significantly inhibited by replacing extracellular Na + with impermeable NMDG + or by blocking non-selective cation channels after drug treatment (8,16). A patchclamp study in pig urinary bladder myocytes has shown that muscarinic receptor stimulation causes Ca…”