Department of Pharmacology

Molecular and Cellular Pharmacology

Hierarchical study of biofunctions that includes the analysis of molecules, cells, and tissues
  • Study of bradycardia at the molecular level
  • Simulations of cardiac excitation and conduction
  • Drug-ion channel interactions
Molecular and Cellular Pharmacology
The laboratory was founded in 1965 under Professor Sentaro Nagasaki. It has since been run by Professors Masayuki Okagawa, Toyoharu Imaizumi, Hiroshi Wada and finally Yoshihisa Kurachi.

Basic research from the molecular to organ level to understand electrical properties of the heart

Cardiac function is maintained by a pump action that keeps the blood constantly circulating. The pump action depends on electric propagation that is regulated by changes in the cell membrane potential. And the membrane potential is regulated by the flow of ions through ion channels and ion transporters. Many ion transporters have been found to have familial genetic mutations, and these mutations are associated with a number of cardiac dysfunctions such as arrhythmia. Therefore, we have been studying the role of ion channels on cardiac function.

Ion channels are useful drug targets for various diseases. However, during drug development, many experimental drugs have disqualifying effects on cardiac function such as cardiac arrhythmia. Thus, cardiotoxicity studies examining the drug effects on ion channels are essential. We are investigating the interactions of multiple channel agonists using a wide range of techniques.

The heart is a hierarchical system in which ion channels are at the molecular level. The networking of multiple ion channels is crucial for function at the cellular level. Then the electrical communication between cells is responsible for high level heart function. To comprehensively understand all layers, it is necessary to elucidate the relationship of the hierarchies. Computer simulations with mathematical models to study the propagation of action potentials within multiple myocardial cells are often used. However, cell morphology, ion channel localization and other spatial factors are not well considered. We are developing new simulations that giver deeper consideration of the cell structure to study electrical conduction and arrhythmias. Our goal is to use these simulations to understand how the heart functions at multiple hierarchical levels.