RT Journal Article
SR Electronic
T1 Molecular Heterogeneity of the Voltage-Gated Fast Transient Outward K<sup>+</sup> Current, <em>I</em><sub>Af</sub>, in Mammalian Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8004
OP 8014
DO 10.1523/JNEUROSCI.21-20-08004.2001
VO 21
IS 20
A1 Sacha A. Malin
A1 Jeanne M. Nerbonne
YR 2001
UL http://www.jneurosci.org/content/21/20/8004.abstract
AB Recently, we identified four kinetically distinct voltage-gated K+ currents, IAf,IAs,IK, andISS, in rat superior cervical ganglion (SCG) neurons and demonstrated thatIAf and IAs are differentially expressed in type I (IAf,IK,ISS), type II (IAf,IAs,IK,ISS), and type III (IK,ISS) SCG cells. In addition, we reported that IAf is eliminated in most (∼70%) SCG cells expressing Kv4.2W362F, a Kv4 subfamily-specific dominant negative. The molecular correlate(s) of the residualIAf, as well as that ofIAs,IK, andISS, however, are unknown. The experiments here were undertaken to explore the role of Kv1 α-subunits in the generation of voltage-gated K+currents in SCG neurons. Using the Biolistics Gene Gun, cDNA constructs encoding a Kv1 subfamily-specific dominant negative, Kv1.5W461F, and enhanced green fluorescent protein (EGFP) were introduced into SCG neurons. Whole-cell recordings from EGFP-positive Kv1.5W461F-expressing cells revealed a selective decrease in the percentage of type I cells and an increase in type III cells, indicating that IAf is gated by Kv1 α-subunits in a subset of type I SCG neurons.IAf is eliminated in all SCG cells expressing both Kv1.5W461F and Kv4.2W362F.IAf τdecay values in Kv1.5W461F-expressing and Kv4.2W362F-expressing type I cells are significantly different, revealing that Kv1 and Kv4 α-subunits encode kinetically distinct IAf channels. Expression of Kv1.5W461F increases excitability by decreasing action potential current thresholds and converts phasic cells to adapting or tonic firing. Interestingly, the molecular heterogeneity ofIAf channels has functional significance because Kv1- and Kv4-encoded IAf play distinct roles in the regulation of neuronal excitability.