Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle

Abstract

The urinary bladder pressure during micturition consists of two components: an initial, phasic component and a subsequent, sustained component. To investigate the excitation mechanisms underlying the sustained pressure, we recorded from membranes of isolated detrusor cells from the pig, which can be used as a model for human micturition. Parasympathomimetic agents promptly evoke a large transient inward current, and subsequently during its continuous presence, oscillating inward currents of relatively small amplitudes are observed. The two types of inward current are considered to cause the phasic and sustained pressure rises, respectively. Ionic substitution and applications of channel blockers revealed that Ca(2+)-activated Cl(-) channels were responsible for the large transient and oscillating inward currents. Furthermore, the inclusion of guanosine 5'-O-(2-thiodiphosphate) in the patch pipette indicates that both inward currents involve G proteins. However, applications of heparin in the patch pipette and of xestospongin C in the bathing solution suggest a signaling pathway other than inositol 1,4,5-trisphosphate (IP(3)) operating in the inward current oscillations, unlike the initial transient inward current. This IP(3)-independent inward current oscillation system required both sustained Ca(2+) influx from the extracellular space and Ca(2+) release from the intracellular stores. These two requirements are presumably SKF-96365-sensitive cation channels and ryanodine receptors, respectively. Experiments with various Ca(2+) concentrations suggested that Ca(2+) influx from the extracellular space plays a major role in pacing the oscillatory rhythm. The fact that distinct mechanisms underlie the two types of inward current may help in development of clinical treatments of, for example, urinary incontinence and residual urine volume control.

Does Phospholipase C Mediate Muscarinic Receptor-Induced Rat Urinary Bladder Contraction?

“…Taken together, the available data clearly show that muscarinic receptors in the bladder can couple to PLC activation (An et al, 2002;Kories et al, 2003;Schneider et al, 2004b;Kajioka et al, 2005) but do not support a major role for such activation in mediating bladder contraction induced by muscarinic receptor agonists. In contrast, undisputed roles exist for an influx of extracellular calcium through voltage-dependent channels (Ikeda et al, 1999;Schneider et al, 2004a,b) and for activation of a rho kinase (Peters et al, 2006) in mediating bladder contraction.…”

“…In contrast, undisputed roles exist for an influx of extracellular calcium through voltage-dependent channels (Ikeda et al, 1999;Schneider et al, 2004a,b) and for activation of a rho kinase (Peters et al, 2006) in mediating bladder contraction. Moreover, calcium release from intracellular stores mediated by a ryanodine receptor may also play a role (Kajioka et al, 2005). …”

“…Muscarinic receptor subtypes can couple to a range of signal transduction pathways, and the primary signaling of M 3 receptors is thought to occur by stimulation of a phospholipase C (PLC) to generate inositol-1,4,5-triphosphate (IP 3 ) and diacylglycerol (Caulfield, 1993). Muscarinic receptor coupling to PLC activation and IP 3 formation in the mammalian urinary bladder also has been reported (An et al, 2002;Kories et al, 2003;Schneider et al, 2004b;Kajioka et al, 2005).…”

Levcromakalim and MgGDP Activate Small Conductance ATP-Sensitive K+ Channels of K+ Channel Pore 6.1/Sulfonylurea Receptor 2A in Pig Detrusor Smooth Muscle Cells: Uncoupling of cAMP Signal Pathways

“…The procedures are essentially the same as previously used for detection of canonical transient receptor potential channels (Asano et al, 1999;Kajioka et al, 2005). Total RNA was isolated from pig detrusor using the RNeasy purification kit (QIAGEN, Tokyo, Japan).…”

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

“…release and suggested that this type of Cl − channel is responsible for muscarinic receptor-induced depolarization (17).…”