KV4.1 channels
| Channel name | KV4.1 |
| Description | Voltage-gated potassium channel, A-type potassium current |
| Other names | mShal1 |
| Molecular information | Human: 647aa, NM_004979, chr. Xp11.23,2 KCND1 (see ′Comments′), GeneID: 3750, PMID: 1072922112 |
| Mouse: 651aa, NM_008423, chr. X | |
| Rat: 650aa, XM_217601 (predicted), chr. Xq13 | |
| Associated subunits | KChIP1 increases KV4.1 current densities, accelerates inactivation time course and recovery from inactivation, and shifts steady-state inactivation to more depolarized potentials3,4 |
| Functional assays | Patch-clamp, two-electrode voltage-clamp |
| Current | Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A-type and attributable to coexpression of KV4.2 and KV4.1 subunits5; subthreshold transient A currents in rat brain6 |
| Conductance | ∼6pS (main unitary conductance under physiological conditions)4,7 |
| Ion selectivity | PNa/PK < 0.01 |
| Activation | Voltage, Va = –47.9 mV; ka = 24.2 mV (assuming a fourth-order Boltzmann function)7 |
| Inactivation | Vh = –69 mV; kh = 4.8 mV; τh1 = 22 ms (20 mV); τh2 = 86 ms (20 mV); τh3 = 368 ms (20 mV)7 (see “Comments”) |
| Activators | None |
| Gating inhibitors | None |
| Blockers | 4-Aminopyridine (9 mM)1,7, tetraethyammonium (> 10 mM)1 |
| Radioligands | None |
| Channel distribution | Fetal, infant, and adult brain; colon, heart, lung, stomach, testis, liver, kidney, thyroid gland, pancreas, pulmonary artery8,9,10 |
| Physiological functions | Not established |
| Mutations and pathophysiology | Not established |
| Pharmacological significance | Not established |
| Comments | The Kv4.1 (KCND1) gene is encoded by at least 6 exons2—the first exon encodes the protein from the N terminus through S5 into the P-region, whereas the remainder of the protein is encoded by exons 2–6; kinetic properties depend on the expression system, recording configuration, and the presence of auxiliary subunits (KChIPs)4,11; mammalian Shal-related family |
aa, amino acids; chr., chromosome.
↵1. Pak MD, Baker K, Covarrubias M, Butler A, Ratcliffe A, and Salkoff L (1991) mShal, a subfamily of A-type K+ channel cloned from mammalian brain. Proc Natl Acad Sci USA 88:4386-4390
↵2. Isbrandt D, Leicher T, Waldschutz R, Zhu X, Luhmann U, Michel U, Sauter K, and Pongs O (2000) Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents ITO and ISA. Genomics 64:144-154
↵3. Nakamura TY, Nandi S, Pountney DJ, Artman M, Rudy B, and Coetzee WA (2001) Different effects of the Ca2+-binding protein, KChIP1, on two Kv4 sub-family members, Kv4.1 and Kv4.2. FEBS Lett 499:205-209
↵4. Beck EJ, Bowlby M, An WF, Rhodes KJ, and Covarrubias M (2002) Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein. J Physiol 538:691-706
↵5. Song WJ, Tkatch T, Baranauskas G, Ichinohe N, Kitai ST, and Surmeier DJ (1998) Somatodendritic depolarization-activated potassium currents in rat neo-striatal cholinergic interneurons are predominantly of the A type and attributable to coexpression of Kv4.2 and Kv4.1 subunits. J Neurosci 18:3124-3137
↵6. Serodio P and Rudy B (1998) Differential expression of Kv4 K+ channel subunits mediating sub-threshold transient K+ (A-type) currents in rat brain. J Neurophysiol 79:1081-1091
↵7. Jerng HH, Shahidullah M, and Covarrubias M (1999) Inactivation gating of Kv4 potassium channels: molecular interactions involving the inner vestibule of the pore. J Gen Physiol 113:641-660
↵8. UniGeneCluster Hs0.55276; OMIM no. 300281
↵9. Davies AR and Kozlowski RZ (2001) Kv channel subunit expression in rat pulmonary arteries. Lung 179:147-161
↵10. Brahmajothi MV, Morales MJ, Liu S, Rasmusson RL, Campbell DL, and Strauss HC (1996) In situ hybridization reveals extensive diversity of K+ channel mRNA in isolated ferret cardiac myocytes. Circ Res 78:1083-1089
↵11. Beck E, and Covarrubias M (2001) Preferential modulation of closed-state inactivation in Kv4 K+ channels. Biophys J 81:867-883
↵12. Isbrandt D, Leicher T, Waldschutz R, Zhu X, Luhmann U, Michel U, Sauter K, and Pongs O (2000) Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents ITO and ISA. Genomics 64:144-154