ZD7288 and mibefradil inhibit the myogenic heartbeat in Daphnia magna indicating its dependency on HCN and T-type calcium ion channels

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Molecular & integrative physiology, 2018-08, Vol.222, p.36-42
• Main Authors: Pirtle, Thomas J., Carr, Troy L., Khurana, Tanisha, Meeker, Grace
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - pharmacology; Calcium Channels, T-Type - drug effects; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Cyclic Nucleotide-Gated Cation Channels - drug effects; Daphnia - physiology; Daphnia magna; Dose-Response Relationship, Drug; HCN channel; Heart; Heart Rate - drug effects; Mibefradil; Mibefradil - administration & dosage; Mibefradil - pharmacology; Myogenic; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; T-type Ca2+ channel; ZD7288
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/j.cbpa.2018.04.009

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.