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

Shunichi Kajioka, Shinsuke Nakayama, Haruhiko Asano, Alison F. Brading

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 Ca2+-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 (IP3) operating in the inward current oscillations, unlike the initial transient inward current. This IP 3-independent inward current oscillation sys-tem required both sustained Ca2+ 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 Ca2+ concentrations suggested that Ca2+ 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume288
Issue number1 57-1
DOIs
Publication statusPublished - Jan 1 2005
Externally publishedYes

Fingerprint

Ryanodine Receptor Calcium Release Channel
Muscarinic Receptors
Smooth Muscle
Urinary Bladder
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Urination
Extracellular Space
Pressure
Membranes
Parasympathomimetics
Residual Volume
Inositol 1,4,5-Trisphosphate
Urinary Incontinence
GTP-Binding Proteins
Heparin
Cations
Swine
Urine

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle. / Kajioka, Shunichi; Nakayama, Shinsuke; Asano, Haruhiko; Brading, Alison F.

In: American Journal of Physiology - Cell Physiology, Vol. 288, No. 1 57-1, 01.01.2005.

Research output: Contribution to journalArticle

@article{6d944b627219489c8b6fcc64a3ef0081,
title = "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 Ca2+-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 (IP3) operating in the inward current oscillations, unlike the initial transient inward current. This IP 3-independent inward current oscillation sys-tem required both sustained Ca2+ 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 Ca2+ concentrations suggested that Ca2+ 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.",
author = "Shunichi Kajioka and Shinsuke Nakayama and Haruhiko Asano and Brading, {Alison F.}",
year = "2005",
month = "1",
day = "1",
doi = "10.1152/ajpcell.00161.2004",
language = "English",
volume = "288",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "1 57-1",

}

TY - JOUR

T1 - Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle

AU - Kajioka, Shunichi

AU - Nakayama, Shinsuke

AU - Asano, Haruhiko

AU - Brading, Alison F.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - 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 Ca2+-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 (IP3) operating in the inward current oscillations, unlike the initial transient inward current. This IP 3-independent inward current oscillation sys-tem required both sustained Ca2+ 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 Ca2+ concentrations suggested that Ca2+ 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.

AB - 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 Ca2+-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 (IP3) operating in the inward current oscillations, unlike the initial transient inward current. This IP 3-independent inward current oscillation sys-tem required both sustained Ca2+ 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 Ca2+ concentrations suggested that Ca2+ 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.

UR - http://www.scopus.com/inward/record.url?scp=10644250809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10644250809&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00161.2004

DO - 10.1152/ajpcell.00161.2004

M3 - Article

VL - 288

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 1 57-1

ER -