Korean J Urol.  2004 Jun;45(6):585-591.

The Effects of Botulinum Toxin-A on Calcium Channel and KDR Channel of the Detrusor Muscle in Rat Bladder Body

• Myung SC
• Song ES
• Keum EM
• Lee MY
• Kim KD

Abstract

PURPOSE: Botulium toxin-A (BoTx A) is useful in treating detrusor-sphincter dyssynergia, detrusor hyperreflexia, and refractory overactive bladder. Only the blocking action of acetycholine (ACh) release from nerve endings is the well known aspect of the action mechanism. The aim of this study is to investigate the effects of BoTx A on the detrusor muscle itself.
MATERIALS AND METHODS
Sprague-Dawley rats were divided into 3 groups: the control group, the low dose injection group (1unit/ml of BoTx A, 0.5cc), and the high dose injection group (5units/ml of BoTx A, 0.5cc). All rats were either injected with normal saline (control group) or BoTx A (injection groups). Ten days after injection, a strip of the detrusor muscle was harvested. Contraction and relaxation responses of the strips were measured by an isometric force transducer. Contractions were induced by various concentrations of ACh, bethanechol, phenylephrine (PE), high concentrations of potassium (35, 70, 105, 140mM), tetraethylammonium (TEA, 0.1, 1, 10mM), 4-aminopyridine (4-AP, a delayed rectifier K+ antagonist, 0.1, 1, 10mM), and Bay K8644 (a L-type voltage dependent calcium channel opener, 0.1, 1, 10mM). The results were analyzed by ANOVA and the Student's t test.
RESULTS
Contractions of the strips were noted when concentrations were above 1mM for TEA and above 0.1mM for 4-AP. A high dose injection as well as a low dose injection of BoTx A had no significant effects on the Ach or bethanechol-induced contractions of the strips compared to the control group. Denervation supersensitivity was not found in the injection groups after the Ach and bethanechol treatments, but the contractility was decreased in high concentrations of potassium (70, 105, 100mM), TEA (10mM), 4-AP (10mM), and Bay K8644 in both the high and low dose injection groups. There was no significant difference in the decrease of contractility between the high and low dose groups with the exception of the Bay K8644 1M treatment.
CONCLUSIONS
BoTx seems to have some direct effects on decreasing the contractility of the detrusor muscle by increasing the delayed rectifier K+ channel activity and decreasing the L-type voltage dependent calcium channel activity.

Keyword

Botulinum toxin type A; Bladder; Calcium channel; Delayed rectifier potassium channel

MeSH Terms

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
4-Aminopyridine
Animals
Ataxia
Bethanechol
Botulinum Toxins, Type A
Calcium Channels*
Calcium*
Denervation
Nerve Endings
Phenylephrine
Potassium
Rats*
Rats, Sprague-Dawley
Reflex, Abnormal
Relaxation
Tea
Tetraethylammonium
Transducers
Urinary Bladder*
Urinary Bladder, Overactive
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
4-Aminopyridine
Bethanechol
Botulinum Toxins, Type A
Calcium
Calcium Channels
Phenylephrine
Potassium
Tea
Tetraethylammonium