Calcium-Activated Chloride Currents Prolongs the Duration of Contractions in Pregnant Rat Myometrial Tissue
Tóm tắt
We investigated the importance of pharmacologically blocking calcium-activated chloride (ICl(Ca)) and L-type calcium currents on isometric contractions of strips of D21 pregnant rat myometrial tissue, while simultaneously measuring the electrical activity of the tissue strips with extracellular contact electrodes. When measured with contact electrodes, the duration of the spiking activity directly reflects the duration of the tissue-level plateau potential. We correlated the number of spikes, durations of spiking activity, and the spiking frequencies with changes of the area under the force curves as a function of exposure to low doses of anthracene–9-carboxylate (9-AC, a non-specific Cl channel blocker), chlorotoxin (a specific ICl(Ca) blocker) and nifedipine (an L-type calcium channel blocker). The area under the force curve was measured only during spiking electrical activity, thereby separating pharmacological effects on tissue relaxation from those that modulate force production. Blocking chloride channels reduced impulse, shortened the duration of spiking activity, and reduced the number of spikes generated in each contraction. This was observed without a change in the frequency of spike production or a reduction of peak force. Nifedipine reduced impulse, shortened the duration of spiking activity, and reduced the number of spikes. In contrast to chloride channel blockade, nifedipine reduced maximum spike frequency and peak force. Taken together, our data suggest that blocking L-type calcium channels reduces impulse directly by reducing peak force, and indirectly by reducing activation of ICl(Ca), which shortens the duration of the contraction.
Tài liệu tham khảo
Shmygol A, Blanks AM, Bru-Mercier G, Gullam JE, Thornton S. Control of uterine Ca2+ by membrane voltage: toward understanding the excitation-contraction coupling in human myometrium. Ann N Y Acad Sci. 2007;1101:97–109.
Okabe K, Inoue Y, Kawarabayashi T, Kajiya H, Okamoto F, Soeda H. Physiological significance of hyperpolarization-activated inward currents (Ih) in smooth muscle cells from the circular layers of pregnant rat myometrium. Pflugers Arch. 1999;439(1–2):76–85.
Pressman EK, Tucker JA Jr, Anderson NC Jr, Young RC. Morphologic and electrophysiologic characterization of isolated pregnant human myometrial cells. Am J Obstet Gynecol. 1988;159(5):1273–1279.
Young RC. Myocytes, myometrium, and uterine contractions. Ann N Y Acad Sci. 2007;1101:72–84.
Kuriyama H, Suzuki H. Changes in electrical properties of rat myometrium during gestation and following hormonal treatments. J Physiol. 1976;260(2):315–333.
Mollard P, Mironneau J, Amedee T, Mironneau C. Electro-physiological characterization of single pregnant rat myometrial cells in short-term primary culture. Am J Physiol. 1986;250(1 pt 1): C47–C54.
Coleman HA, Parkington HC. Induction of prolonged excitability in myometrium of pregnant guinea-pigs by prostaglandin F2 alpha. J Physiol. 1988;399:33–47.
Wilde DW, Marshall JM. Effects of tetraethylammonium and 4-aminopyridine on the plateau potential of circular myometrium from the pregnant rat. Biol Reprod. 1988;38(4):836–845.
Parkington HC, Coleman HA. Ionic mechanisms underlying action potentials in myometrium. Clin Exp Pharmacol Physiol. 1988;15(9):657–665.
Kaya T, Guvenal T, Karadas B, Cetin A, Soydan AS. Effects of 5-nitro–2-(3-phenylpropylamino) benzoic acid, anthracene–9-carboxylate, and zaprinast on endothelin–1-induced contractions of pregnant rat myometrium. Eur J Obstet Gynecol Reprod Biol. 2002;105(2):114–119.
Yarar Y, Cetin A, Kaya T. Chloride channel blockers 5-nitro–2-(3-phenylpropylamino) benzoic acid and anthracene–9-car-boxylic acid inhibit contractions of pregnant rat myometrium in vitro. J Soc Gynecol Investig. 2001;8(4):206–209.
Jones K, Shmygol A, Kupittayanant S, Wray S. Electrophysio-logical characterization and functional importance of calcium-activated chloride channel in rat uterine myocytes. Pflugers Arch. 2004;448(1):36–43.
Pacaud P, Loirand G, Gregoire G, Mironneau C, Mironneau J. Calcium-dependence of the calcium-activated chloride current in smooth muscle cells of rat portal vein. Pflu-gers Arch. 1992;421(2–3):125–130.
Piper AS, Greenwood IA. Anomalous effect of anthracene–9-carboxylic acid on calcium-activated chloride currents in rabbit pulmonary artery smooth muscle cells. Br J Pharmacol. 2003;138(1):31–38.
Hogg RC, Wang Q, Large WA. Effects of Cl channel block-ers on Ca-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein. Br J Pharmacol. 1994;111(4):1333–1341.
Dalton S, Gerzanich V, Chen M, Dong Y, Shuba Y, Simard JM. Chlorotoxin-sensitive Ca2+-activated Cl-channel in type R2 reactive astrocytes from adult rat brain. Glia. 2003;42(4):325–339.
Lamont RF, Khan KS, Beattie B, et al. The quality of nifedi-pine studies used to assess tocolytic efficacy: a systematic review. J Perinat Med. 2005;33(4):287–295.
Longo M, Jain V, Vedernikov YP, Hankins GD, Garfield RE, Saade GR. Effects of L-type Ca(2+)-channel blockade, K(+)(ATP)-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour. Mol Hum Reprod. 2003;9(3):159–164.
Ruttner Z, Ivanics T, Slaaf DW, Reneman RS, Toth A, Ligeti L. In vivo monitoring of intracellular free calcium changes during uterine activation by prostaglandin f(2alpha) and oxytocin. J Soc Gynecol Investig. 2002;9(5):294–298.