Muscarinic stimulation increases basal Ca2+ and inhibits spontaneous Ca2+ transients in murine colonic myocytes

被引:29
作者
Bayguinov, O [1 ]
Hagen, B [1 ]
Sanders, KM [1 ]
机构
[1] Univ Nevada, Sch Med, Dept Physiol & Cell Biol, Reno, NV 89557 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2001年 / 280卷 / 03期
关键词
calcium puffs; nonselective cation current; muscarinic receptors; enteric neurotransmission;
D O I
10.1152/ajpcell.2001.280.3.C689
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Localized Ca2+ transients in isolated murine colonic myocytes depend on Ca2+ release from inositol 1,4,5-trisphosphate (IP3) receptors. Localized Ca2+ transients couple to spontaneous transient outward currents (STOCs) and mediate hyperpolarization responses in these cells. We used confocal microscopy and whole cell patch-clamp recording to investigate how muscarinic stimulation, which causes formation of IP3, can suppress Ca2+ transients and STOCs that might override the excitatory nature of cholinergic responses. ACh (10 muM) reduced localized Ca2+ transients and STOCs, and these effects were associated with a rise in basal cytosolic Ca2+. These effects of ACh were mimicked by generalized rises in basal Ca2+ caused by ionomycin (250-500 nM) or elevated external Ca2+ (6 mM). Atropine (10 muM) abolished the effects of ACh. Pretreatment of cells with nicardipine (1 muM), or Cd2+ (200 muM) had no effect on responses to ACh. An inhibitor of phospholipase C, U-73122, blocked Ca2+ transients and STOCs but did not affect the increase in basal Ca2+ after ACh stimulation. Xestospongin C (Xe-C; 5 muM), a membrane-permeable antagonist of IP3 receptors, blocked spontaneous Ca2+ transients but did not prevent the increase of basal Ca2+ in response to ACh. Gd3+ (10 muM), a nonselective cation channel inhibitor, prevented the increase in basal Ca2+ after ACh and increased the frequency and amplitude of Ca2+ transients and waves. Another inhibitor of receptor-mediated Ca2+ influx channels, SKF-96365, also prevented the rise in basal Ca2+ after ACh and increased Ca2+ transients and development of Ca2+ waves. FK-506, an inhibitor of FKBP12/IP3 receptor interactions, had no effect on the rise in basal Ca2+ but blocked the inhibitory effects of increased basal Ca2+ and ACh on Ca2+ transients. These results suggest that the rise in basal Ca2+ that accompanies muscarinic stimulation of colonic muscles inhibits localized Ca2+ transients that could couple to activation of Ca2+ activated K+ channels and reduce the excitatory effects of ACh.
引用
收藏
页码:C689 / C700
页数:12
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