J Korean Med Sci.  2003 Oct;18(5):701-706. 10.3346/jkms.2003.18.5.701.

Inhibitory Effects of Potassium Channel Blockers on Carbachol-induced Contraction in Rat Detrusor Muscle

• Oh SJ
• Ahn SC

• KMID: 1130042
• DOI: http://doi.org/10.3346/jkms.2003.18.5.701

Abstract

We present accidental findings that potassium channel blockers, such as tetraethyl-ammonium (TEA) or 4-aminopyridine (4-AP), inhibit the sustained tonic contraction induced by carbachol in rat detrusor muscle strips. The relatively lower concentrations (<2 mM) of TEA and 4-AP inhibited phasic and tonic contractions induced by 5 micrometer carbachol, whilst the relatively higher concentrations of TEA and 4-AP (>5 mM) potentiated phasic contractions. The potentiation of phasic contraction was not observed in nicardipine pretreated condition. In nicardipine pretreated condition, the concentration-response curves for the negative inotropic effect of potassium channel blockers were shifted to the right by the increasing concentration of carbachol from 0.5 micrometer to 5 micrometer. IC50 was changed significantly from 0.19 to 0.64 mM (TEA) and from 0.21 to 0.96 (4-AP). Such inhibitory effects were also observed in Ca2+ depleted condition, where 0.1 mM EGTA and 1 micrometer thapsigargin were added into Ca2+ free solution. In conclusion, inhibitory effects of potasssium channel blockers on carbachol-induced contraction may be ascribed to the direct inhibition of receptor-agonist binding.

Keyword

Rat; Urinary Tract; Bladder; Carbachol; Tetraethylammonium; 4-Aminopyridine

MeSH Terms

4-Aminopyridine/pharmacology
Animals
Bladder/metabolism
Calcium/chemistry/metabolism
Calcium Channel Blockers/pharmacology
Carbachol/*pharmacology
Dose-Response Relationship, Drug
Female
Guinea Pigs
Inhibitory Concentration 50
Male
Mice
Muscle Contraction/*drug effects
Muscles/drug effects/metabolism/*pathology
Nicardipine/pharmacology
Potassium Channel Blockers/*pharmacology
Protein Binding
Rabbits
Rats
Rats, Sprague-Dawley
Support, Non-U.S. Gov't
Tetraethylammonium/pharmacology
Vasodilator Agents/pharmacology