Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Neurogastroenterol Motil. 2010 Dec;22(12):e353-63. doi: 10.1111/j.1365-2982.2010.01596.x.
R-type Ca(2+) channels are expressed by myenteric neurons in the guinea pig ileum but the specific function of these channels is unknown.
In the present study, we used intracellular electrophysiological techniques to determine the function of R-type Ca(2+) channels in myenteric neurons in the acutely isolated longitudinal musclemyenteric plexus. We used immunohistochemical methods to localize the Ca(V)2.3 subunit of the R-type Ca(2+) channel in myenteric neurons. We also studied the effects of the non-selective Ca(2+) channel antagonist, CdCl₂ (100 μmol L⁻¹), the R-type Ca(2+) channel blockers NiCl₂ (50 μmol L⁻¹) and SNX-482 (0.1 μmol L⁻¹), and the N-type Ca(2+) channel blocker x-conotoxin GVIA (CTX 0.1 μmol L⁻¹) on action potentials and fast and slow excitatory postsynaptic potentials (fEPSPs and sEPSPs) in S and AH neurons in vitro.
Ca(V)2.3 co-localized with calretinin and calbindin in myenteric neurons. NiCl₂ and SNX-482 reduced the duration and amplitude of action potentials in AH but not S neurons. NiCl₂ inhibited the afterhyperpolarization in AH neurons. x-conotoxin GVIA, but not NiCl₂, blocked sEPSPs in AH neurons. NiCl₂ and SNX-482 inhibited cholinergic, but not cholinergic/purinergic, fEPSPs in S neurons.
These data show that R-type Ca(2+) channels contribute to action potentials, but not slow synaptic transmission, in AH neurons. R-type Ca(2+) channels contribute to release of acetylcholine as the mediator of fEPSPs in some S neurons. These data indicate that R-type Ca(2+) channels may be a target for drugs that selectively modulate activity of AH neurons or could alter fast synaptic excitation in specific pathways in the myenteric plexus.
R 型钙通道在豚鼠回肠的肌间神经元中表达，但这些通道的具体功能尚不清楚。
在本研究中，我们使用细胞内电生理技术来确定在急性分离的纵向肌-肌间神经丛中的肌间神经元中 R 型钙通道的功能。我们使用免疫组织化学方法来定位 R 型钙通道的 Ca(V)2.3 亚基在肌间神经元中的位置。我们还研究了非选择性钙通道拮抗剂 CdCl₂（100 μmol L⁻¹）、R 型钙通道阻滞剂 NiCl₂（50 μmol L⁻¹）和 SNX-482（0.1 μmol L⁻¹）以及 N 型钙通道阻滞剂 x-conotoxin GVIA（CTX 0.1 μmol L⁻¹）对 S 和 AH 神经元的动作电位以及快速和慢速兴奋性突触后电位（fEPSP 和 sEPSP）的影响。
Ca(V)2.3 与肌间神经元中的 calretinin 和 calbindin 共定位。NiCl₂和 SNX-482 降低了 AH 神经元但不影响 S 神经元的动作电位的持续时间和幅度。NiCl₂抑制了 AH 神经元的后超极化。x-conotoxin GVIA 而非 NiCl₂阻断了 AH 神经元中的 sEPSP。NiCl₂和 SNX-482 抑制了 S 神经元中的胆碱能而非胆碱能/嘌呤能 fEPSP。
这些数据表明，R 型钙通道有助于 AH 神经元中的动作电位，但不参与慢突触传递。R 型钙通道有助于某些 S 神经元中乙酰胆碱的释放，作为 fEPSP 的递质。这些数据表明，R 型钙通道可能是一种药物的靶点，该药物可以选择性地调节 AH 神经元的活性，或改变肌间神经丛中特定途径的快速突触兴奋。
