Staff and specialities
Professor: Hiroshi MATSUURA
Associate Professor: Mariko OMATSU-KANBE
Senior Assistant Professor: Futoshi TOYODA
Senior Assistant Professor: Wei-Guang DING
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,.