BACKGROUND: Pharmacological manipulation of the anal sphincter is hampered by a lack of specificity. This study aimed to determine differences in the role of intracellular and extracellular calcium in the development of tone and agonist-induced contractions between internal anal sphincter (IAS) and rectal circular muscle which might allow targeted manipulation. METHODS: Smooth muscle strips from the IAS and rectal circular muscle of 24 Large White pigs were mounted for isometric tension recording in a superfusion organ bath in the presence of different perfusates. RESULTS: IAS developed tone and spontaneous activity that were abolished by nifedipine, which also reduced contractions to noradrenaline to 72 per cent of control values. Rectal smooth muscle developed spontaneous activity but no tone. Nifedipine abolished the activity and reduced contractions to carbachol to 17 per cent of control. Contractile activity was abolished in both tissues in calcium-free solution. Transient exposure to a high calcium concentration reloaded the stores, and the ability of agonists to release stored calcium was tested after 3 min in calcium-free solution. In IAS, noradrenaline contraction was 76 per cent of control and in rectal circular muscle carbachol contraction was 57 per cent of control. Store loading was prevented by nifedipine in rectal smooth muscle but not IAS. Cyclopiazonic acid reduced store filling in both tissues. CONCLUSION: Agonist-induced contraction of IAS is largely due to release of stored calcium and L-type calcium channels are not needed for store filling. Rectal circular smooth muscle depends more on extracellular calcium and uses L-type calcium channels for agonist-induced contraction and store filling. These differences suggest that targeted manipulation may be possible in patients with anorectal disorders.
BACKGROUND: Pharmacological manipulation of the anal sphincter is hampered by a lack of specificity. This study aimed to determine differences in the role of intracellular and extracellular calcium in the development of tone and agonist-induced contractions between internal anal sphincter (IAS) and rectal circular muscle which might allow targeted manipulation. METHODS: Smooth muscle strips from the IAS and rectal circular muscle of 24 Large Whitepigs were mounted for isometric tension recording in a superfusion organ bath in the presence of different perfusates. RESULTS: IAS developed tone and spontaneous activity that were abolished by nifedipine, which also reduced contractions to noradrenaline to 72 per cent of control values. Rectal smooth muscle developed spontaneous activity but no tone. Nifedipine abolished the activity and reduced contractions to carbachol to 17 per cent of control. Contractile activity was abolished in both tissues in calcium-free solution. Transient exposure to a high calcium concentration reloaded the stores, and the ability of agonists to release stored calcium was tested after 3 min in calcium-free solution. In IAS, noradrenaline contraction was 76 per cent of control and in rectal circular muscle carbachol contraction was 57 per cent of control. Store loading was prevented by nifedipine in rectal smooth muscle but not IAS. Cyclopiazonic acid reduced store filling in both tissues. CONCLUSION: Agonist-induced contraction of IAS is largely due to release of stored calcium and L-type calcium channels are not needed for store filling. Rectal circular smooth muscle depends more on extracellular calcium and uses L-type calcium channels for agonist-induced contraction and store filling. These differences suggest that targeted manipulation may be possible in patients with anorectal disorders.