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. Author manuscript; available in PMC: 2011 Apr 30.
Published in final edited form as: Circ Res. 2010 Mar 25;106(8):1342–1350. doi: 10.1161/CIRCRESAHA.109.213132

Table 1.

Developmental effects of pharmacological modulators of ion channel function.

target agent type delivery [drug] n phenotypes
VGSC tetrodotoxin inhibitor bath solution 500µm 74

  • Normal heart tube formation (68/70).

  • Total neuromuscular paralysis (70/70)
bath solution 500µm 26

  • Normal nkx2.5 expression (24/26).
microinjection 1mM 99

  • Normal heart tube formation (99/99).

  • Total neuromuscular paralysis (93/99).
VGSC lidocaine inhibitor bath solution 500µm 200

  • Normal heart tube formation (200/200).

  • Epiboly defects at higher doses.
VGSC anemone
toxin II		 activator bath solution 10µM 25

  • Normal nkx2.5 expression (20/25).
microinjection 100µM 50

  • Normal heart tube formation (50/50).

  • Convulsions, tonic contraction elicited with mechanical stimulation.
VGSC veratridine activator bath solution 100µM 34

  • Normal nkx2.5 expression (26/34).
microinjection 1mM 50

  • Normal heart tube formation (50/50).

  • Convulsions, tonic contraction elicited with mechanical stimulation.
VGSC; ERG flecainide inhibitor bath solution 400µm 46

  • Normal heart tube formation (45/46).

  • Bradycardia, 2:1 heart block, less frequent silent ventricle or irregular atrial rhythm on day 2 in morphologically normal hearts, similar to ERG block alone (45/45).
bath solution 400µm 29

  • Normal nkx2.5 expression (23/29).
LTCC nisoldipine inhibitor bath solution 10µm 100

  • Normal heart tube formation (100/100).

  • No heart beat, circulation at any stage.

  • Atrium, ventricle, outflow tract morphologically normal through day 2.5.

  • Cardiac looping normal through day 2.5.

  • Markedly decreased GFP intensity (∼cmlc2 promoter activity) at all stages.
LTCC/
TTCC		 mibefradil inhibitor bath solution 250µm 77

  • Normal heart tube formation (77/77).

  • Bradycardia, weak contractility on day 2 in morphologically normal hearts (77/77).
ERG E-4031 inhibitor bath solution 250µm 93

  • Normal heart tube formation (93/93).

  • Arrhythmias on day 2 in morphologically normal hearts:

    • bradycardia, silent ventricle (85/93)

    • irregular atrial rhythm, silent ventricle (7/93)

    • silent heart (1/93)

VGSC = voltage-gated sodium channel, LTCC = L-type calcium channel, TTCC = T-type calcium channel, ERG = ether-a-go-go related gene potassium channel. For bath immersion, embryos were dechorionated and placed in drug solutions by the 64 cell stage. For microinjection, 3 nanoliters of drug solution were injected in 2 different locations of the yoke sac of 1–4 cell stage embryos. Cardiac lineage specification assessed by in situ hybridization for nkx2.5 at 8 somites. Differentiation assessed by heart tube formation and heart beating in Tg(cmlc2:GFP) embryos at 28–30 h.p.f. See methods for additional details.