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A‐type K + channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons
Author(s) -
Carrasquillo Yarimar,
Burkhalter Andreas,
Nerbonne Jeanne M.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.229013
Subject(s) - neuroscience , hippocampal formation , biology , ion channel , chemistry , receptor , biochemistry
Key points• A‐type K + currents, I A , are key determinants of neuronal excitability. Previous studies suggest critical roles for voltage‐gated K + (Kv) channel pore‐forming (α) subunits of the Kv4 subfamily in the generation of neuronal I A channels. • The experiments here examined directly the functional roles of Kv4.2, Kv4.3 and Kv1.4 in the regulation of the intrinsic excitability and the firing properties of mature cortical pyramidal (CP) neurons. • The results demonstrate roles for Kv4.2, Kv4.3 and Kv1.4 in the generation of I A channels and show that Kv4.2‐, Kv4.3‐ and Kv1.4‐encoded I A channels play distinct roles in regulating the intrinsic excitability and the firing properties of CP neurons. • These findings demonstrate previously unappreciated molecular and functional diversity of I A in central neurons, insights that will contribute importantly to future studies focused on determining the mechanisms underlying the alterations in neuronal excitability in epilepsy and other neurological disorders.Abstract Rapidly activating and rapidly inactivating voltage‐gated A‐type K + currents, I A , are key determinants of neuronal excitability and several studies suggest a critical role for the Kv4.2 pore‐forming α subunit in the generation of I A channels in hippocampal and cortical pyramidal neurons. The experiments here demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of I A channels in mature cortical pyramidal (CP) neurons and that Kv4.2‐, Kv4.3‐ and Kv1.4‐encoded I A channels play distinct roles in regulating the intrinsic excitability and the firing properties of mature CP neurons. In vivo loss of Kv4.2, for example, alters the input resistances, current thresholds for action potential generation and action potential repolarization of mature CP neurons. Elimination of Kv4.3 also prolongs action potential duration, whereas the input resistances and the current thresholds for action potential generation in Kv4.3 −/− and WT CP neurons are indistinguishable. In addition, although increased repetitive firing was observed in both Kv4.2 −/− and Kv4.3 −/− CP neurons, the increases in Kv4.2 −/− CP neurons were observed in response to small, but not large, amplitude depolarizing current injections, whereas firing rates were higher in Kv4.3 −/− CP neurons only with large amplitude current injections. In vivo loss of Kv1.4, in contrast, had minimal effects on the intrinsic excitability and the firing properties of mature CP neurons. Comparison of the effects of pharmacological blockade of Kv4‐encoded currents in Kv1.4 −/− and WT CP neurons, however, revealed that Kv1.4‐encoded I A channels do contribute to controlling resting membrane potentials, the regulation of current thresholds for action potential generation and repetitive firing rates in mature CP neurons.