Pirtle Thomas J, Carr Troy L, Khurana Tanisha, Meeker Grace
Biology Department, The College of Idaho, USA.
Biology Department, The College of Idaho, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2018 Aug;222:36-42. doi: 10.1016/j.cbpa.2018.04.009. Epub 2018 Apr 21.
Daphnia magna heartbeat is myogenic-originating within the animal's heart. However, the mechanism for this myogenic automaticity is unknown. The mechanism underlying the automaticity of vertebrate myogenic hearts involves cells (pacemaker cells), which have a distinct set of ion channels that include hyperpolarization activated cyclic nucleotide-gated (HCN) and T-type calcium ion channels. We hypothesized that these ion channels also underlie the automatic myogenic heartbeat of Daphnia magna. The drugs, ZD7288 and mibefradil dihydrochloride, block HCN and T-type calcium ion channels respectively. Application of these drugs, in separate experiments, show that they inhibit the heartbeat of Daphnia magna in a dose-dependent manner. Calculation of the percent difference between the heart rate of pretreatment (before drug application) and heart rate following drug application (post-treatment) allowed us to graph a dose-response curve for both ZD7288 and mibefradil, revealing that ZD7288 produces a greater effect on decreasing heart rate. This indicates the HCN ion channels play a foremost role in generating Daphnia magna heartbeat. Our results show conclusively that HCN and T-type calcium ion channels underlie the automatic myogenic heartbeat in Daphnia magna-and suggest a conserved mechanism for generating myogenic heartbeat within the animal kingdom. Thus, Daphnia magna represents a credible model system for further exploration of cardiac physiology.
大型溞的心跳起源于动物自身的心脏，属于肌源性。然而，这种肌源性自动节律的机制尚不清楚。脊椎动物肌源性心脏自动节律的潜在机制涉及细胞（起搏细胞），这些细胞具有一组独特的离子通道，包括超极化激活的环核苷酸门控（HCN）通道和T型钙离子通道。我们推测这些离子通道也是大型溞肌源性自动心跳的基础。药物ZD7288和盐酸米贝地尔分别阻断HCN通道和T型钙离子通道。在单独的实验中应用这些药物，结果表明它们以剂量依赖的方式抑制大型溞的心跳。通过计算预处理（用药前）心率与用药后（治疗后）心率之间的百分比差异，我们得以绘制出ZD7288和盐酸米贝地尔的剂量反应曲线，结果显示ZD7288在降低心率方面产生的影响更大。这表明HCN离子通道在产生大型溞心跳方面起着首要作用。我们的结果确凿地表明，HCN通道和T型钙离子通道是大型溞肌源性自动心跳的基础，并且提示了动物界产生肌源性心跳的一种保守机制。因此，大型溞是进一步探索心脏生理学的可靠模型系统。
