米羅加巴林（Mirogabalin）是一種電壓門控的鈣離子（Cav）通道阻滯劑，已被證實會影響該通道的 α2δ-1 亞基。而 GV-58 則被認為是 N-和 P/Q 型鈣離子電流的激活劑。然而，米羅加巴林和 GV-58 對各種類型的細胞膜離子通道的大小、門控和/或滯後效應的影響程度仍未得到徹底探索。可能的情況是，它們不僅可以阻止電壓門控的鈣離子（Cav）通道，還可以調節其他類型的離子通道。因此，我打算研究米羅加巴林和 GV-58 對電壓門控鈉離子通道電流（INa）的影響。首先，我使用標準膜片鉗電流記錄來檢測老鼠腦垂腺腫瘤細胞（GH3）中存在的 INa是否受添加不同濃度的米羅加巴林/ GV-58 影響。其次，我在老鼠腦垂腺腫瘤細胞(GH3)中使用一系列去極化脈衝，以顯示米羅加巴林/ GV-58 對瞬時鈉離子電流 INa（T）失活的恢復效應。最後，我使用兩種不同的電壓鉗協議來檢測它們對復甦型鈉離子電流（INa（R））和窗口型鈉離子電流（INa（W））的影響。根據我們的實驗結果，我發現米羅加巴林和 GV-58 在濃度依賴性方面差別地影響了 INa 的峰值（瞬時 INa（T））和持續（延遲 INa（L））。此外，米羅加巴林延長了一系列去極化脈衝中 INa（T）失活的恢復時間。相反，GV-58 緩解了失活速率。最後，米羅加巴林/GV-58 有效地抑制/增加了由上升或下降的電壓鉗協議引發的復甦型鈉離子電流（INa（R））和窗口型鈉離子電流（INa（W））。總之，細胞暴露於米羅加巴林/GV-58 不僅可以影響鈣離子（Cav），還可以調節鈉離子通道（Nav）。

Mirogabalin is a voltage-gated Ca2+ (Cav) channels blocker which is recognized to affect α2δ-1 subunit of the channel. And GV-58 is recognized to be an activator of N- and P/Q-type Ca2+ currents. However, to what extent both mirogabalin and GV-58 modifies the magnitude, gating, and/or hysteresis of various types of plasmalemmal ionic currents remains largely unexplored. It would be possible that they might not only block Cav channels, but also regulate other types of ionic channels. Therefore, we intended to investigate the effect of mirogabalin and GV-58 on voltage-gated sodium current (INa) occurs. First, we used standard patch-clamp current recordings to detect the INa residing in pituitary tumor (GH3) cells with or without the addition of different mirogabalin/GV-58 concentrations. Second, we used a train of depolarizing pulses in GH3 cell in order to show the effect of mirogabalin/GV-58 on recovery of INa(T) inactivation. Finally, we used two different voltage-clamp protocols to recognize their effect on resurgent sodium current (INa(R)) and window sodium current (INa(W)). According to our experimental results, we found that mirogabalin and GV-58 were differentially effective at modifying the peak (transient, INa(T)) and sustained (late, INa(L)) components of INa in a concentration-dependent manner. Moreover, mirogabalin prolonged the recovery of INa(T) inactivation in a train of depolarizing pulses. GV-58, on the contrary, relieved the inactivation rate. At last, mirogabalin/GV-58 effectively suppressed/increased INa(W) and INa(R) evoked by ascending or descending Vramp. As above, cell exposure to mirogabalin/GV-58 could not only affect Cav channels, but also regulate Nav channel.

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