Koh Sang Don, Jun Jae Yeoul, Kim Tae Wan, Sanders Kenton M
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
J Physiol. 2002 May 1;540(Pt 3):803-14. doi: 10.1113/jphysiol.2001.014639.
Interstitial cells of Cajal (ICC) provide pacemaker activity in some smooth muscles. The nature of the pacemaker conductance is unclear, but studies suggest that pacemaker activity is due to a voltage-independent, Ca(2+)-regulated, non-selective cation conductance. We investigated Ca(2+)-regulated conductances in murine intestinal ICC and found that reducing cytoplasmic Ca(2+) activates whole-cell inward currents and single-channel currents. Both the whole-cell currents and single-channel currents reversed at 0 mV when the equilibrium potentials of all ions present were far from 0 mV. Recordings from on-cell patches revealed oscillations in unitary currents at the frequency of pacemaker currents in ICC. Voltage-clamping cells to -60 mV did not change the oscillatory activity of channels in on-cell patches. Depolarizing cells with high external K(+) caused loss of resolvable single-channel currents, but the oscillatory single-channel currents were restored when the patches were stepped to negative potentials. Unitary currents were also resolved in excised patches. The single-channel conductance was 13 pS, and currents reversed at 0 mV. The channels responsible were strongly activated by 10(-7) M Ca(2+), and 10(-6) M Ca(2+) reduced activity. The 13 pS channels were strongly activated by the calmodulin inhibitors calmidazolium and W-7 in on-cell and excised patches. Calmidazolium and W-7 also activated a persistent inward current under whole-cell conditions. Murine ICC express Ca(2+)-inhibited, non-selective cation channels that are periodically activated at the same frequency as pacemaker currents. This conductance may contribute to the pacemaker current and generation of electrical slow waves in GI muscles.
Cajal间质细胞（ICC）在某些平滑肌中提供起搏活动。起搏电导的性质尚不清楚，但研究表明，起搏活动是由于一种电压非依赖性、Ca(2+)调节的非选择性阳离子电导所致。我们研究了小鼠肠道ICC中的Ca(2+)调节电导，发现降低细胞质Ca(2+)会激活全细胞内向电流和单通道电流。当所有存在离子的平衡电位都远离0 mV时，全细胞电流和单通道电流均在0 mV处反转。对细胞贴附片的记录显示，单位电流以ICC中起搏电流的频率振荡。将细胞电压钳制在-60 mV不会改变细胞贴附片上通道的振荡活动。用高细胞外K(+)使细胞去极化会导致可分辨的单通道电流消失，但当将贴片钳制到负电位时，振荡的单通道电流会恢复。在切除的贴片中也分辨出了单位电流。单通道电导为13 pS，电流在0 mV处反转。所涉及的通道被10(-7) M Ca(2+)强烈激活，而10(-6) M Ca(2+)会降低活性。在细胞贴附片和切除的贴片中，13 pS通道被钙调蛋白抑制剂氯米帕明和W-7强烈激活。氯米帕明和W-7在全细胞条件下也会激活持续的内向电流。小鼠ICC表达Ca(2+)抑制的非选择性阳离子通道，这些通道以与起搏电流相同的频率周期性激活。这种电导可能有助于起搏电流的产生以及胃肠道肌肉中电慢波的产生。
