Download Jürgen R. Schwarz

Alexander von Humboldt Foundation Conference
«Technologies of the 21st century: biological, physical, informational and social aspects»
Saint-Petersburg, Russia, September 27-29, 2005
PHYSIOLOGY OF SUBTHRESHOLD CURRENTS
Jürgen R. Schwarz
Institute of Applied Physiology, University of Hamburg
Information processing within the brain involves the generation of action potentials
which are responsible for fast communication between nerve cells. Action potentials have a
short duration and are generated by a transient influx of Na+ and a delayed outflow of K+
through voltage-gated ion channels. In addition to these canonical ion channels, nerve cells
are equipped with a large number of voltage-gated and Ca2+-gated ion channels which are
able to modulate their excitability. These ion channels are activated within the subthreshold
potential range. This property enables them not only to influence the threshold potential, they
also change the action potential duration, induce various forms of afterhyperpolarizations and
set the interspike interval. By modulating the shape of action potentials and spiking patterns
they are able to change information processing in neurons, thus contributing to neuronal
plasticity. The Ih and the M-current belong to the most important threshold currents. Ih is a
pacemaker current, mediated by hyperpolarization-activated cyclic-nucleotide-gated cation
channels (HCN). The M-current is mediated by members of the family of voltage-gated
KCNQ channels. One important function of M-currents is the induction of frequency
adaptation. The current mediated by ether-à-go-go-related gene K+ channels (erg) is
predominantly known as a cardiac current which takes part in repolarizing the heart action
potential. However, erg channels have recently been shown to also modulate neuronal
electrical activity. Further members of subthreshold currents are the A-type current mediated
by voltage-gated K+ channels of the Kv4 family and Ca2+-gated SK channels. Both types of
current are involved in the modulation of the frequency of action potential firing, i.e. the
precise timing of the interspike interval. In addition to the usage of slices for patch-clamping
or of heterologous expression systems an overview of transgenic animal models used to study
the properties of e.g. KCNQ and HCN channels will be given. Thereafter the molecular
properties and physiology of the ion channels mediating the different types of subthreshold
currents will be presented as well as an insight into their complex subunit composition.
Special emphasis will be laid upon the description of a M-like current in the rat node of
Ranvier as well as on the presentation of the physiology of erg K channels in various types of
neurons and neuroendocrine cells.
Prof. Dr. Jürgen R. Schwarz, M.D.
Institut für Angewandte Physiologie
Zentrum für experimentelle Medizin
Universitätsklinikum Eppendorf
Martinistraße 52, D-20246 Hamburg
Tel.: 040-42803-2190; Fax: 040-42803-9127
E-mail: [email protected]