Ca2+sparks and BK currents in gallbladder myocytes: role in CCK-induced response

American Journal of Physiology - Gastrointestinal and Liver Physiology - Tập 282 Số 1 - Trang G165-G174 - 2002
Marı́a J. Pozo1, Guillermo J. Pérez2, Mark T. Nelson2, Gary M. Mawe3,2
1Department of Physiology, University of Extremadura, 10071 Cáceres, Spain; and
2Department of Pharmacology, and
3Department of Anatomy and Neurobiology, University of Vermont, Burlington, Vermont 05405

Tóm tắt

We sought to elucidate the regulation of gallbladder smooth muscle (GBSM) excitability by localized Ca2+release events (sparks) and large-conductance Ca2+-dependent (BK) channels by determining whether sparks exist in GBSM and, if so, whether they activate BK channels. Sparks were identified in isolated GBSM loaded with fluo 4. Each spark was associated with a transient outward current, suggesting communication of ryanodine receptor (RyR) channels with BK channels. This was confirmed by the inhibition of outward currents with iberiotoxin (100 nM), thapsigargin (200 nM), and ryanodine (10 μM). In current clamp mode, the transient BK currents were associated with brief membrane hyperpolarizations (10.9 ± 1.3 mV). Because transient BK currents could dampen GBSM excitability, we tested whether CCK attenuates these events. CCK (10 nM) reduced the amplitude and frequency of transient BK currents, and subsequent caffeine application restored transient BK current activity. These results support the concept that RyRs and BK channels contribute to the regulation of GBSM excitability and that CCK can act in part by inhibiting this pathway.

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Tài liệu tham khảo

Alcón S, 2001, Anal Pharmacol, 2, 48

10.1152/ajpcell.2000.279.1.C126

10.1152/ajpcell.2001.280.3.C689

10.1113/jphysiol.1986.sp016333

10.1038/316345a0

10.1038/361315a0

10.1146/annurev.physiol.61.1.85

10.1152/ajpcell.1997.273.6.C2090

10.1038/35038011

10.1126/science.8235594

10.1085/jgp.115.5.653

10.1085/jgp.110.3.257

10.1085/jgp.109.5.647

10.1083/jcb.52.3.690

10.1152/ajpcell.2000.278.5.C1031

10.1152/physrev.1997.77.3.699

Galvez A, 1990, J Biol Chem, 265, 11083, 10.1016/S0021-9258(19)38560-6

10.1161/01.RES.67.2.525

10.1161/01.RES.83.11.1104

10.1046/j.1365-2818.1999.00599.x

10.1152/ajpcell.2001.280.3.C481

10.1007/BF00550873

10.1085/jgp.92.2.145

10.1152/ajpcell.2000.279.5.C1528

10.1152/ajpcell.2000.278.2.C235

10.1152/ajpcell.1998.274.6.C1755

10.1111/j.1469-7793.2001.0315i.x

10.1038/379455a0

10.1111/j.1469-7793.1998.211br.x

10.1126/science.7754383

10.1093/oxfordjournals.jbchem.a021780

10.1126/science.270.5236.633

10.1152/ajpcell.1995.268.4.C799

10.1016/0167-0115(96)00023-7

10.1085/jgp.113.2.229

10.1152/ajpcell.1987.253.3.C364

10.1016/0167-0115(92)90060-8

10.1038/372231a0

10.1152/ajpcell.1993.265.6.C1552

10.1085/jgp.116.6.845

10.1085/jgp.113.2.215

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American Journal of Physiology - Gastrointestinal and Liver Physiology

Tập 282 Số 1

G165-G174

Thông tin tác giả