Stargazer mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear. We describe here a novel gene, Cacng2, whose expression is disrupted in two stargazer alleles. It encodes a 36-kD protein (stargazin) with structural similarity to the gamma subunit of skeletal muscle voltage-gated calcium (Ca2+) channels. Stargazin is brain-specific and, like other neuronal Ca2+-channel subunits, is enriched in synaptic plasma membranes. In vitro, stargazin increases steady-state inactivation of alpha1 class A Ca2+ channels. The anticipated effect in stargazer mutants, inappropriate Ca2+ entry, may contribute to their more pronounced seizure phenotype compared with other mouse absence models with Ca2+-channel defects. The discovery that the stargazer gene encodes a gamma subunit completes the identification of the major subunit types for neuronal Ca2+ channels, namely alpha1, alpha2delta, beta and gamma, providing a new opportunity to understand how these channels function in the mammalian brain and how they may be targeted in the treatment of neuroexcitability disorders.

Ion channels and transporters, key elements in sperm-egg signaling and environmental sensing, are essential for fertilization. External cues and components from the outer envelopes of the egg influence sperm ion permeability and behavior. Combining in vivo measurements of membrane potential, intracellular ions, and second messengers with new molecular approaches and reconstitution strategies are revealing how sperm ion channels participate in motility, sperm maturation, and the acrosome reaction. Sperm are tiny differentiated terminal cells unable to synthesize proteins and difficult to characterize electrophysiologically. Spermatogenic cells, the progenitors of sperm, have become useful tools for probing sperm ion channels since they are larger and molecular biology techniques can be applied. These complementary strategies are opening new avenues to determine how sperm ion channels function in gamete signaling.

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