Staff and specialities

Professor:  Hiroshi MATSUURA
   Cardiac physiology 
Associate Professor:  Mariko OMATSU-KANBE
   Cell physiology
Senior Assistant Professor:  Futoshi TOYODA
   Cardiac physiology
Senior Assistant Professor:  Wei-Guang DING
   Cardiac physiology

Outline of the department

We have been investigating the function of ion channels and transporters in 
the heart to clarify their roles in cardiac function by using 
electrophysiological, pharmacological and molecular biological methods. In 
addition, we have been conducting experiments to elucidate molecular basis for 
the regulation of ion channels by neurotransmitters, hormones, intracellular 
molecules and exogenous drugs that affect cardiac electrical activity. 

At present we are conducting the following research projects:
1) Ionic basis underlying the spontaneous electrical activity in sinoatrial 
   (SA) node pacemaker cells in mammalian heart.
   It has been demonstrated that the spontaneous action potentials in mammalian 
   SA node cells are generated by the interaction of multiple ionic currents, 
   such as rapidly and slowly activating components of the delayed rectifier K+ 
   current (IKr and IKs, respectively), hyperpolarization-activated cyclic 
   nucleotide-gated (HCN) current, and T- and L-type Ca2+ currents. We have 
   characterized respective roles of IKr and IKs in the development of 
   spontaneous pacemaker activity in mammalian SA node cells. In addition, we 
   have cloned the HCN4 gene from guinea-pig heart (in collaboration with Dr. 
   Takahiro Isono, Central Research Laboratory, Shiga University of Medical 
   Science) and analyzed its function by expressing in mammalian cells.

2) The regulatory mechanism of IKs in mammalian cardiac myocytes.
   IKs is essential for normal repolarization of cardiac myocytes and mutations 
   in genes encoding IKs channels (KCNQ1 and KCNE1) have been associated with 
   long QT syndrome, an inherited cardiac arrhythmia characterized by abnormal 
   ventricular repolarization and a high risk for sudden cardiac death. We have 
   identified novel signaling mechanisms for regulation of IKs in mammalian 
   cardiac myocytes. These include a potentiation of IKs by P2Y receptor 
   stimulation and an inhibition of IKs by endogenous membrane phospholipid 
   phosphatidylinositol 4,5-bisphophate (PIP2). We are aiming at clarifying the 
   significance of various regulatory mechanisms or molecules for IKs under 
   physiological and pathophysiological conditions.

   Furthermore the store-operated Ca2+ entry, the predominant process for Ca2+ 
   supply from the extracellular spaces, has been examined in rat brown 
   adipocytes. We found that extracellular ATP not only mobilizes Ca2+ from the 
   intracellular stores but also exerts a potent inhibitory effect on the store-
   operated Ca2+ entry process. The experiments are currently undertaken to 
   elucidate the cellular and molecular mechanisms for the regulation of the 
   store-operated Ca2+ entry by various signaling molecules that modulate 
   intracellular Ca2+ levels,.