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The large and diverse family of ion channels known as potassium (K+) channels controls neurotransmitter release, the resting membrane potential, action potential waveform and duration, rhythmic firing patterns, and pacemaking activities of neurons. Among the various voltage-gated K+ (Kv) channel types, Kv3 subfamily subunits (Kv3.1-Kv3.4) form homotetrameric and heterotetrameric K+ channels that exhibit distinct biophysical characteristics, including high activation thresholds, rapid activation and deactivation kinetics, as well as relatively large conductances. These characteristics allow neurons to fire brief action potentials at high frequencies exceeding 500 Hz. Despite being present throughout the nervous system, Kv3-type subunits are only expressed in certain neuronal subpopulations found in particular parts of the brain.

Creative Biolabs can offer in vitro assays and related products to meet the needs of Kv3 drug discovery:

Overview of Kv3

Wider action potentials and less rapid afterhyperpolarization are caused by the absence or pharmacological inhibition of Kv3 channels, and these effects together cause a prolonged refractory period and poorer high-frequency firing. Increased Ca2+ influx caused by widened spikes can also boost neurotransmitter release. According to these theories, the cerebellum exhibits graded action potential broadening in parallel fibers and a corresponding reduction in paired-pulse facilitation at the parallel fiber-Purkinje cell synapse when either Kv3.1, Kv3.3, or both subunits are absent. The decrease in paired-pulse facilitation implies that neurotransmitter release is constitutively elevated and that calcium influx is already approaching saturating the release machinery during the first pulse. In Purkinje cells, which express Kv3.4 subunits mostly in dendrites, the basic spike duration doubles and there are fewer spikelets in complex spikes when Kv3.3 subunits are simply absent. Simple spike length is unaffected in Kv3.1 single mutants, supporting the idea that Kv3.1 is not expressed in mature Purkinje cells.

Kv3 Drug Discovery

Neurons can fire repeatedly at high frequencies thanks to the Kv3 channel's wide activation range and quick deactivation kinetics. Given that they seem to be present in the majority of neurons that can fire repetitively at high frequencies, Kv3 channels may have been a widespread solution in vertebrates to the issues caused by high-frequency repeatedly firing. a discovery that would suggest that various neurons use different techniques to accomplish high-frequency repeated firing. Additionally, Kv3 gene products have been found in neurons that are not known to fire rapidly, indicating that Kv3 channels may have additional physiological roles. Kv3 channels are also strongly expressed in presynaptic terminals and axons. Investigations on Kv3 channels' presynaptic role are still ongoing.


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