Differential expression of Kv4 K+ channel subunits mediating subthreshold
transient K+ (A-type) currents in rat brain.
Paulo Serdio and Bernardo Rudy.
Department of Physiology & Neuroscience, Department of Biochemistry, New
York University School of Medicine, 550 First Ave., N.Y., N.Y., 10016. Center
for Neurobiology & Behavior, Columbia University College of Physicians &
Surgeons, New York.
APStracts 4:272N, 1997.
ABSTRACT
The mammalian Kv4 gene subfamily and its Drosophila Shal counterpart encode
proteins that form fast inactivating K+ channels that activate and inactivate
at subthreshold potentials and recover from inactivation at a faster rate than
other inactivating Kv channels. Taken together, the properties of Kv4 channels
compare best with those of low-voltage activating "A-currents" present in the
neuronal somato-dendritic compartment and widely reported across several types
of central and peripheral neurons, as well as the (Ca2+-independent) transient
outward potassium conductance of heart cells (Ito). Three distinct genes have
been identified that encode mammalian Shal homologues (Kv4.1, Kv4.2 and Kv4.3)
of which the latter two are abundant in rat adult brain and heart tissues. The
distribution in the adult rat brain of the mRNA transcripts encoding the three
known Kv4 subunits was studied by in situ hybridization histochemistry. Kv4.1
signals are very faint, suggesting that Kv4.1 mRNAs are expressed at very low
levels, but Kv4.2 and Kv4.3 transcripts appear to be abundant, and each
produces a unique pattern of expression. Although there is overlap expression
of Kv4.2 and Kv4.3 transcripts in several neuronal populations, the dominant
feature is one of differential, and sometimes reciprocal expression. For
example, Kv4.2 transcripts are the predominant form in the caudate-putamen,
pontine nucleus, and several nuclei in the medula, whereas the substantia
nigra pars compacta, the restrosplenial cortex, the superior colliculus, the
raphe and the amygdala express mainly Kv4.3. Some brain structures contain
both Kv4.2 and Kv4.3 mRNAs but each dominates in distinct neuronal
subpopulations. For example, in the olfactory bulb Kv4.2 dominates in granule
cells and Kv4.3 in periglomerular cells. In the hippocampus Kv4.2 is the most
abundant isoform in CA1 pyramidal cells, whereas only Kv4.3 is expressed in
interneurons. Both are abundant in CA2-CA3 pyramidal cells and in granule
cells of the dentate gyrus which also express Kv4.1. In the dorsal thalamus
strong Kv4.3 signals are seen in several lateral nuclei, whereas medial nuclei
express Kv4.2 and Kv4.3 at moderate to low levels. In the cerebellum Kv4.3,
but not Kv4.2, is expressed in Purkinje cells and molecular layer
interneurons. In the cerebellar granule cell layer, the reciprocity between
Kv4.2 and Kv4.3 is observed in subregions of the same neuronal population. In
fact, the distribution of Kv4 channel transcripts in the cerebellum defines a
new pattern of compartmentation of the cerebellar cortex, and the first one
involving molecules directly involved in signal processing.
Received 20 May 1997; accepted in final form 23 September 1997.
APS Manuscript Number J424-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997