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Scand J Urol Nephrol. 2007;41(4):270-7.

Intracellular calcium in hypertrophic smooth muscle from rat urinary bladder.

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  • 1Department of Experimental Medical Science, Lund University, Lund, Sweden.

Abstract

OBJECTIVE:

To explore whether infravesical outlet obstruction is associated with alterations in calcium activation of detrusor smooth muscle.

MATERIAL AND METHODS:

Outlet obstruction was created by partial ligature of the urethra in female rats. Western blotting was performed using an antibody against the cytoplasmatic region of the alpha1c subunit of the L-type Ca2+ channel. Intracellular calcium was measured using Fura-2 in detrusors that had been obstructed for 10 days and activated by high K+ concentrations at different extracellular Ca2+ concentrations. The rate of force development after rapid opening of L-type Ca2+ channels was measured in contractions initiated by flash photolysis of nifedipine in Ca2(+)-containing depolarizing solution.

RESULTS:

Bladder weight increased from 62 +/- 3 to 254 +/- 43 mg after 10 days of obstruction. Expression of the alpha1c subunit increased after 3 days and continued to increase until it was about fourfold greater after 10 days; however, it had not increased further at 6 weeks. This change was reversible after removal of obstruction. Activation with K+ produced a stable force at different extracellular Ca2+ concentrations, with no difference in response between controls and rats that had been obstructed for 10 days. Intracellular Ca2+ concentrations were lower in the obstructed group, showing that the calcium sensitivity of the contraction force had increased. The delay between the opening of L-type channels and the onset of contraction was longer in obstructed detrusors.

CONCLUSIONS:

Growth of detrusor muscle following obstruction is accompanied by attenuated calcium transients following activation, despite upregulation of L-type Ca2+ channels. The Ca2+ sensitivity of contraction was increased in obstructed detrusors. We suggest that the decreased surface: volume ratio in hypertrophic smooth muscle cells is partly involved in the lowered Ca2+ transients. The increases in L-type calcium channels and in calcium sensitivity may be compensatory mechanisms.

PMID:
17763216
[PubMed - indexed for MEDLINE]
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