Sympathetic neurons modulate the beat rate of pluripotent cell-derived cardiomyocytes in vitro.
Although stem cell-derived cardiomyocytes have great potential for the therapy of heart failure, it is unclear whether their function after grafting can be controlled by the host sympathetic nervous system, a component of the autonomic nervous system (ANS). Here we demonstrate the formation of functional connections between rat sympathetic superior cervical ganglion (SCG) neurons and pluripotent (P19.CL6) cell-derived cardiomyocytes (P19CMs) in compartmentalized co-culture, achieved using photolithographic microfabrication techniques. Formation of synapses between sympathetic neurons and P19CMs was confirmed by immunostaining with antibodies against β-3 tubulin, synapsin I and cardiac troponin-I. Changes in the beat rate of P19CMs were triggered after electrical stimulation of the co-cultured SCG neurons, and were affected by the pulse frequency of the electrical stimulation. Such changes in the beat rate were prevented when propranolol, a β-adrenoreceptor antagonist, was added to the culture medium. These results suggest that the beat rate of differentiated cardiomyocytes can be modulated by electrical stimulation of connected sympathetic neurons.
Graduate School of Frontier Sciences, The University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba, Japan. takeuchi@bmpe.k.u-tokyo.ac.jp
Akimasa
A
Takeuchi
Kenta
K
Shimba
Masahide
M
Mori
Yuzo
Y
Takayama
Hiroyuki
H
Moriguchi
Kiyoshi
K
Kotani
Jong-Kook
JK
Lee
Makoto
M
Noshiro
Yasuhiko
Y
Jimbo
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000295:instrumentation; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D046210:Microfluidic Analytical Techniques; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000502:physiology; D049490:Systems Biology
D000319:Adrenergic beta-Antagonists; D011433:Propranolol