Changes in calcium-dependent potassium channels of isolated smooth muscle cells of the bladder in rats with experimental diabetes
Kryshtal' DA, Paduraru OM, Boldyriev OI, Kit OIu, Rekalov VV, Shuba IaM
- O.O.Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
- International Center of Molecular Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz57.03.025
Abstract
Activation of large conductance Ca2+-dependent potassium channels (BK channels) influences repolarization of the action potential and the level of the resting potential of detrusor smooth muscle cells (SMC). Overactive bladder syndrome (OBS) is one of the complications of diabetes. Here using whole-cell patch clamp technique we show sizable reduction of depolarization-evoked BK current (T) and decrease in the amplitude and frequency of spontaneous transient outward currents (STOCs) in isolated SMC from detrusor of rats with streptozocin-induced diabetes compared to control animals. Under the diabetes L_ density at step depolarization to +50 mV decreased from control value of 15.0±0.4 pA/pF to 10.0і0.5 pA/pF, whereas the mean values of the STOCs’ frequency and amplitude at holding potential -20 mV were reduced from 12.0±1.5 Hz to 2.4±0.6 Hz and from 0.9±0.1 pA/pF to 0.5±0.1 pA/pF, respectively. Using real time RT-PCR it was found that the expression of mRNA for the BK-channel primary pore-forming KCa 1.1-subunit increases under the diabetes, whilst that for the auxiliary BKC (31-subunit decreases. It is concluded that the observed changes in the BK-channel currents can enhance excitability of the detrusor SMCs thereby promoting myogenic OBS. However, further studies are needed to determine how the decrease in BK p1 expression under the diabetes impairs functional properties of BK channels and to establish possible changes in calcium signals that modulate channel activation.
Keywords:
bladder, detrusor, smooth muscles, diabetes mel-litus, calcium dependent potassium channels, BK-channels
References
- Boldyrev OI, Sotkis HV, Kuliieva IeM, Vladymyrova IA, Filippov IB, Skryma R, Prevars'ka N, Shuba IaM. Expression of the cold receptor TRPM8 in the smooth muscles of the seminal ejaculatory ducts in rats. . Fiziol Zh. 2009. 55, N 5. P. 17-27.
- Brading A.F. Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function . J. Physiol. 2006. 570. P. 13-22.
CrossRef
PubMed PubMedCentral
- Christ G.J., Hodges S. Molecular mechanisms of detrusor and corporal myocyte contraction: identifying targets for pharmacotherapy of bladder and erectile dysfunction . Brit. J. Pharmacol. 2006. 147. P. S41-S55.
CrossRef
PubMed PubMedCentral
- Heppner T.J., Bonev A.D., Nelson M.T. Ca(2+)-acti-vated K+ channels regulate action potential repolarization in urinary bladder smooth muscle . Amer. J. Physiol 1997. 273, N 1. P. C110-C117.
CrossRef
PubMed
- Hristov K.L., Cui X., Brown S.M., Kellett W.F. Petkov G.V. Stimulation of beta3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca2+-activated K+ channels . Ibid. 2008. 295,N 5. P. C1344-C1353.
CrossRef
PubMed PubMedCentral
- Jaggar J.H., Porter V.A., Lederer W.J., Nelson M.T. Calcium sparks in smooth muscle . Amer. J. Physiol. 2000. 278, N 2. P. C235-C256.
CrossRef
PubMed
- McManus O.B., Helms L.M., Pallanck L., Ganetzky B., Swanson R., Leonard R.J. Functional role of the beta subunit of high conductance calcium-activated potassium channels . Neuron. 1995. 14. P. 645-650.
CrossRef
- Meredith A.L., Thorneloe K.S., Werner M.E., Nelson M.T. Aldrich W.T. Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-acti-vated K+ channel . J. Biol. Chem. 2004. 279. P. 36746-36752.
CrossRef
PubMed
- Orio P., Rojas P., Ferreira G., Latorre R. New disguises for an old channel: MaxiK channel beta-sub-units . News Physiol. Sci. 2002. 17. P. 156-161.
CrossRef
PubMed
- Petkov G.V., Bonev A.D., Heppner T.J., Brenner R., Aldrich R.W., Nelson M.T. Beta 1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle . J. Physiol. 2001. 537. P. 443-452.
CrossRef
PubMed PubMedCentral
- Roxburgh C, Cook J., Dublin N. Anticholinergic drugs versus other medications for overactive bladder syndrome in adults . Cochrane Database Syst. Rev. 2007. 3, N 4. P. CD00319.
CrossRef
- Soloviev A., Tishkin S., Ivanova I., Zelensky S., Dosenko V., Kyrychenko S., Moreland R.S. Functional and molecular consequences of ionizing irradiation on large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells . Life Sci. 2009. 84, N 5-6. P. 164-171.
CrossRef
PubMed
- Toro B., Cox N., Wilson R.J., Garrido-Sanabria E., Stefani E., Toro L., Zarei M.M. KCNMB1 regulates surface expression of a voltage and Ca2+-activated K+ channel via endocytic trafficking signals . Neuroscience. 2006. 142, N 3. P. 661-669.
CrossRef
PubMed
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