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First published online on February 1, 2002.
 Copyright © 2002 by The Physiological Society
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Received December 13, 2001
Accepted after revision January 25, 2002

Heterogeneous expression of KChIP2 isoforms in the ferret heart

Sangita P. Patel1*, Donald L. Campbell2, Michael J. Morales2, and Harold C. Strauss2

1 Department of Physiology and Biophysics, University at Buffalo, SUNY, 124 Sherman Hall, 3435 Main Street, Buffalo, NY, 14214, USA
2 Department of Physiology and Biophysics, University at Buffalo, SUNY, Buffalo, NY, 14214, USA

* To whom correspondence should be addressed. E-mail: sppatel{at}acsu.buffalo.edu.

Kv4 channels are believed to underlie the rapidly recovering cardiac transient outward current (Ito) phenotype. However, heterologously expressed Kv4 channels fail to fully reconstitute the native current. Kv channel interacting proteins (KChIPs) have been shown to modulate Kv4 channel function. To determine the potential involvement of KChIPs in the rapidly recovering Ito, we cloned three KChIP2 isoforms (designated fKChIP2, 2a and 2b) from the ferret heart. Based upon immunoblot data suggesting the presence of a potential endogenous KChIP-like protein in HEK 293, CHO and COS cells but absence in Xenopus oocytes, we coexpressed Kv4.3 and the fKChIP2 isoforms in Xenopus oocytes. Functional analysis showed that while all fKChIP2 isoforms produced a fourfold acceleration of recovery kinetics compared to Kv4.3 expressed alone, only fKChIP2a produced large depolarizing shifts in the V1/2 of steady-state activation and inactivation as seen for the native rapidly recovering Ito. Analysis of RNA and protein expression of the three fKChIP2 isoforms in ferret ventricles showed that fKChIP2b was most abundant and was expressed in a gradient paralleling the rapidly recovering Ito distribution. Ferret KChIP2 and 2a were expressed at very low levels. The ventricular expression distribution suggests that fKChIP2 isoforms are involved in modulation of the rapidly recovering Ito; however, additional regulatory factors are also likely to be involved in generating the native current.




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