Koshimizu T A, Van Goor F, Tomić M, Wong A O, Tanoue A, Tsujimoto G, Stojilkovic S S
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Mol Pharmacol. 2000 Nov;58(5):936-45. doi: 10.1124/mol.58.5.936.
ATP-gated purinergic receptors (P2XRs) are a family of cation-permeable channels that conduct Ca(2+) and facilitate voltage-sensitive Ca(2+) entry in excitable cells. To study Ca(2+) signaling by P2XRs and its dependence on voltage-sensitive Ca(2+) influx, we expressed eight cloned P2XR subtypes individually in gonadotropin-releasing hormone-secreting neurons. In all cases, ATP evoked an inward current and a rise in Ca(2+). P2XR subtypes differed in the peak amplitude of Ca(2+) response independently of the level of receptor expression, with the following order: P2X(1)R < P2X(3)R < P2X(4)R < P2X(2b)R < P2X(2a)R < P2X(7)R. During prolonged agonist stimulation, Ca(2+) signals desensitized with different rates: P2X(3)R > P2X(1)R > P2X(2b)R > P2X(4)R >> P2X(2a)R >> P2X(7)R. The pattern of Ca(2+) response for each P2XR subtype was highly comparable with that of the depolarizing current, but the activation and desensitization rates were faster for the current than for Ca(2+). The P2X(1)R, P2X(3)R, and P2X(4)R-derived Ca(2+) signals were predominantly dependent on activation of voltage-sensitive Ca(2+) influx, both voltage-sensitive and -insensitive Ca(2+) entry pathways equally contributed to Ca(2+) responses in P2X(2a)R- and P2X(2b)R-expressing cells, and P2X(7)R operated as a nonselective pore capable of conducting larger amounts of Ca(2+) independently on the status of voltage-gated Ca(2+) channels. Thus, Ca(2+) signaling by homomeric P2XRs expressed in an excitable cell is subtype-specific, which provides an effective mechanism for generating variable Ca(2+) patterns in response to a common agonist.
三磷酸腺苷（ATP）门控嘌呤能受体（P2XRs）是一类阳离子通透通道家族，可传导Ca(2+)并促进其在可兴奋细胞中通过电压敏感途径内流。为了研究P2XRs介导的Ca(2+)信号传导及其对电压敏感Ca(2+)内流的依赖性，我们在促性腺激素释放激素分泌神经元中分别表达了8种克隆的P2XR亚型。在所有情况下，ATP均可诱发内向电流并使细胞内Ca(2+)浓度（Ca(2+)）升高。P2XR亚型的Ca(2+)反应峰值幅度各不相同，且与受体表达水平无关，顺序如下：P2X(1)R < P2X(3)R < P2X(4)R < P2X(2b)R < P2X(2a)R < P2X(7)R。在长时间激动剂刺激期间，Ca(2+)信号以不同速率脱敏：P2X(3)R > P2X(1)R > P2X(2b)R > P2X(4)R >> P2X(2a)R >> P2X(7)R。每种P2XR亚型的Ca(2+)反应模式与去极化电流的模式高度相似，但电流的激活和脱敏速率比Ca(2+)更快。源自P2X(1)R、P2X(3)R和P2X(4)R的Ca(2+)信号主要依赖于电压敏感Ca(2+)内流的激活，电压敏感和非敏感Ca(2+)进入途径对表达P2X(2a)R和P2X(2b)R的细胞中的Ca(2+)反应贡献相同，并且P2X(7)R作为一种非选择性孔道发挥作用，能够独立于电压门控Ca(2+)通道的状态传导大量Ca(2+)。因此，在可兴奋细胞中表达的同聚体P2XRs介导的Ca(2+)信号传导具有亚型特异性，这为响应共同激动剂产生可变的Ca(2+)模式提供了一种有效机制。
