Muscle and motor-skill dysfunction in a K+ channel-deficient mouse are not due to altered muscle excitability or fiber type but depend on the genetic background

Abstract

The voltage-gated K+ channel Kv3.1 is expressed in skeletal muscle and in GABAergic interneurons in the central nervous system. Hence, the absence of Kv3.1 K+ channels may lead to a phenotype of myogenic or neurogenic origin, or both. Kv3.1-deficient (Kv3.1-/-) 129/Sv mice display altered contractile properties of their skeletal muscles and show poor performance on a rotating rod. In contrast, Kv3.1-/- mice on the (129/Sv x C57BL/6)F1 background display normal muscle properties and perform like wild-type mice. The correlation of poor performance on the rotating rod with altered muscle properties supports the notion that the skeletal muscle dysfunction in Kv3.1-/- 129/Sv mice may be responsible for the impaired motor skills on the rotating rod. Surprisingly, we did not find major differences between wild-type and Kv3.1-/- 129/Sv skeletal muscles in either the resting or action potential, the delayed-rectifier potassium conductance (gK) or the distribution of fast and slow muscle fibers. These findings suggest that the Kv3.1 K+ channel may not play a major role in the intrinsic excitability of skeletal muscle fibers although its absence leads to slower contraction and relaxation and to smaller forces in muscles of 129/Sv Kv3.1-/- mice.

Alcohol Hypersensitivity, Increased Locomotion, and Spontaneous Myoclonus in Mice Lacking the Potassium Channels Kv3.1 and Kv3.3

“…The rotarod test was performed as described previously Sánchez et al, 2000). Briefly, male mice were placed on a rod (8.9 cm long and 3.8 cm in diameter), initially rotating at 5 rpm and accelerating at 10 rpm /min (Rotamex System; Columbus Instruments, Columbus, OH).…”

“…The generation of the Kv3.1 Ϫ/Ϫ mouse on the 129/Sv, C57BL /6, and 129/Sv ϫ C57BL /6 F1 background has been described previously Sánchez et al, 2000). The Kv3.3-encoding gene was inactivated by homologous recombination using a targeting vector in which the region containing the ATG initiation triplet was deleted and replaced with the phosphoglycerate kinase-neomycin resistance cassette inserted in the opposite orientation relative to the direction of transcription of the Kv3.3 gene (Chan, 1997).…”

“…The Kv3.1 single mutant shows increased ␥-and decreased ␦-oscillations and a motor-skill deficit caused by altered muscle contractility and force generation Joho et al, 1997Joho et al, , 1999. The motor-skill deficit is, however, only present in 129/Sv and not in 129/Sv ϫ C57BL/6 F1 mice; i.e., the penetrance of the Kv3.1-null mutation depends strongly on the genetic background (Sánchez et al, 2000). The Kv3.3 single mutant displays no overt phenotype (Chan, 1997).…”

Activation of conventional kinesin motors in clusters by shaw voltage-gated potassium channels

“…We examined the KIF5B distribution pattern in Kv3.1 KO mice, which were published previously (Ho et al, 1997;Sánchez et al, 2000;Hurlock et al, 2009). The KO mice were confirmed with western blotting and PCR-based genotyping (Fig.…”

“…Kv3.1 knockout (KO) mouse line was kindly provided by Dr R. Joho at UT Southwestern Medical Center and have been maintained using a PCR-based genotyping procedure as previously described (Ho et al, 1997;Sánchez et al, 2000;Hurlock et al, 2009). The Kv3.1 KO mice were backcrossed with BL6 for ten generations.…”