Laszlo Roman, Winkler Christoph, Wöhrl Stefan, Wessel Ralf E, Laszlo Sara, Busch Mathias C, Schreieck Jürgen, Bosch Ralph F
Department of Cardiology, University of Tübingen, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2007 Dec;376(4):231-40. doi: 10.1007/s00210-007-0188-0. Epub 2007 Sep 15.
We investigated the effects of a 7-day verapamil pretreatment (VPT, 7.5 mg/kg bodyweight subcutaneously every 12 h) on ionic currents and molecular mechanisms underlying tachycardia-induced early electrical remodeling after 24-h rapid atrial pacing (RAP, 600 bpm) in rabbit atrium. Animals were divided into four groups (n = 6 each group): control (not paced, no verapamil), paced only, verapamil only and verapamil and paced, respectively. VPT doubled ICa,L [7.0 +/- 0.7 pA/pF (control) vs 14.2 +/- 0.6 pA/pF (verapamil only)]. RAP reduced ICa,L by 48% to 3.6 +/- 0.7 pA/pF (paced only). RAP did not affect ICa,L in verapamil-treated animals and averaged 15.3 +/- 0.2 pA/pF (paced and verapamil). RAP resulted in a significant decrease of the expression of the alpha1c subunit (-24.7%) and the beta2A subunit (-13.3%), respectively. VPT led to a similar alteration of subunit expression as RAP ["control" vs "verapamil only", decrease of alpha1c subunit (-25.4%), but no significant change in beta2A subunit expression]. However, after VPT, further diminishment of alpha1c and beta2A subunit expression after rapid atrial pacing was absent. ("verapamil" vs "verapamil and paced", n = 6 both groups). RAP decreased Ito [-45%, 51.5 +/- 3.9 pA/pF (control) vs 26.8 +/- 1.5 pA/pF (paced only)] and was not influenceable by VPT. IK1 was neither affected by RAP nor verapamil pretreatment. Downregulation of alpha1c and beta2A subunit expression and the resulting decay of ICa,L current densities were prevented by verapamil. However, these effects are abolished by multiple other adverse effects of verapamil on atrial electrophysiology.
我们研究了7天维拉帕米预处理（VPT，每12小时皮下注射7.5mg/kg体重）对兔心房24小时快速心房起搏（RAP，600次/分钟）后心动过速诱导的早期电重构潜在离子电流和分子机制的影响。动物分为四组（每组n = 6）：对照组（未起搏，未用维拉帕米）、仅起搏组、仅用维拉帕米组和维拉帕米并用起搏组。VPT使L型钙电流（ICa,L）加倍[7.0±0.7pA/pF（对照组）对14.2±0.6pA/pF（仅用维拉帕米组）]。RAP使ICa,L降低48%至3.6±0.7pA/pF（仅起搏组）。RAP对维拉帕米处理的动物的ICa,L无影响，平均为15.3±0.2pA/pF（起搏并用维拉帕米组）。RAP分别导致α1c亚基（-24.7%）和β2A亚基（-13.3%）表达显著降低。VPT导致亚基表达的改变与RAP相似["对照组"对"仅用维拉帕米组"，α1c亚基降低（-25.4%），但β2A亚基表达无显著变化]。然而，VPT后，快速心房起搏后α1c和β2A亚基表达不再进一步减少。（"维拉帕米组"对"维拉帕米并用起搏组"，两组均n = 6）。RAP降低了瞬时外向钾电流（Ito）[-45%，51.5±3.9pA/pF（对照组）对26.8±1.5pA/pF（仅起搏组）]，且不受VPT影响。内向整流钾电流（IK1）既不受RAP影响，也不受维拉帕米预处理影响。维拉帕米可防止α1c和β2A亚基表达下调以及由此导致的ICa,L电流密度衰减。然而，这些作用被维拉帕米对心房电生理的多种其他不良反应所消除。
