Cloning of a novel component of A-type K + channels operating at
subthreshold potentials with unique expression in heart and brain.
Ser[circumflex]odio, P., E. Vega-Saenz de Miera, and B. Rudy.
Department of Physiology and Neuroscience, New York University Medical
APStracts 3:0005N, 1996.
SUMMARY AND CONCLUSIONS
1. Proteins of the Kv4 or Shal-related subfamily are key components of
transient K + channels (A channels) operating at subthreshold values of the
membrane potential (I SA channels). We have cloned and characterized a new
mammalian Kv4 or Shal-related cDNA (Kv4.3) which predicts a protein with
strong sequence conservation with the other known members of this subfamily.
2. Injection of Kv4.3 transcripts into Xenopus oocytes generates an A type K +
current, with small but physiologically significant differences from the
currents expressed by Kv4.2 and Kv4.1 mRNAs. Kv4.3 currents can be modified to
resemble native I SA s by co-injection with a low molecular weight mRNA
fraction from rat brain which does not express detectable currents on its own.
Particularly striking is a 7-10 fold increase in the rate of recovery from
inactivation, a 5-10 fold increase in current magnitude and a 3-4 fold
increase in sensitivity to 4-amino pyridine (4-AP). 3. In-situ hybridization
histochemistry was used to compare the expression of the three known Kv4
genes. Kv4.2 and Kv4.3 (but not Kv4.1) are abundant in the adult rat brain,
but each displays a specific, but sometimes overlapping pattern of expression.
Moreover, a reciprocal gradient of expression of Kv4.2 and Kv4.3 transcripts
is seen in some brain areas, such as in the pyramidal cell layers of the
hippocampus and the granule cell layer of the cerebellum. Therefore Kv4
proteins may form heteromultimeric channels of distinct subunit composition in
different neurons. Moreover, the results suggest that neurons such as
pyramidal cells in the hippocampus and granule cells in the cerebellum
represent heterogeneous cell populations in terms of their I SA , and hence in
their firing patterns. Kv4.2 and Kv4.3 also display complementary expression
in the heart, with Kv4.3 being more abundant in atria and Kv4.2 in ventricle.
The existence of multiple Kv4 proteins forming channels of variable subunit
combinations helps explain the diversity of I SA channels in neurons.
Received 12 October 1995; accepted in final form 15 December 1995.
APS Manuscript Number J682-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96