Pleiotropic effects of a disrupted K+ channel gene: Reduced body weight, impaired motor skill and muscle contraction, but no seizures

AUTOR(ES)

Ho, Chi Shun

FONTE

The National Academy of Sciences of the USA

RESUMO

To investigate the roles of K+ channels in the regulation and fine-tuning of cellular excitability, we generated a mutant mouse carrying a disrupted gene for the fast activating, voltage-gated K+ channel Kv3.1. Kv3.1−/− mice are viable and fertile but have significantly reduced body weights compared with their Kv3.1+/− littermates. Wild-type, heterozygous, and homozygous Kv3.1 channel-deficient mice exhibit similar spontaneous locomotor and exploratory activity. In a test for coordinated motor skill, however, homozygous Kv3.1−/− mice perform significantly worse than their heterozygous Kv3.1+/− or wild-type littermates. Both fast and slow skeletal muscles of Kv3.1−/− mice are slower to reach peak force and to relax after contraction, consequently leading to tetanic responses at lower stimulation frequencies. Both mutant muscles generate significantly smaller contractile forces during a single twitch and during tetanic conditions. Although Kv3.1−/− mutants exhibit a normal auditory frequency range, they show significant differences in their acoustic startle responses. Contrary to expectation, homozygous Kv3.1−/− mice do not have increased spontaneous seizure activity.

Documentos Relacionados

• Muscle Contraction, its Regulatory Mechanisms
• Effects of development and thyroid hormone on K+ currents and K+ channel gene expression in rat ventricle.
• Reduced K+ Channel Inactivation, Spike Broadening, and After-Hyperpolarization in Kvβ1.1-Deficient Mice with Impaired Learning
• Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2
• Expression and chromosomal localization of a lymphocyte K+ channel gene.