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

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.