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Author(s): David Z. Z. He (corresponding author) [1, 2]; Shuping Jia [1]; Peter Dallos [3] Sensory receptor cells of the mammalian cochlea are morphologically and functionally dichotomized. Inner hair cells [...]

Author(s): M. Charles Liberman [1, 2]; Jiangang Gao [2, 3]; David Z. Z. He [4]; Xudong Wu [3, 5]; Shuping Jia [4]; Jian Zuo (corresponding author) [3] Hearing sensitivity in [...]

The molecular components of store-operated Ca 2+ influx channels (SOCs) in proliferative and migratory vascular smooth muscle cells (VSMCs) are quite intricate with many channels contributing to SOCs. They include the Ca 2+ -selective Orai1 and members of the transient receptor potential canonical (TRPC) channels, which are activated by the endoplasmic reticulum Ca 2+ sensor STIM1. The scaffolding protein Homer assembles SOC complexes, but its role in VSMCs is not well understood. Here, we asked whether these SOC components and Homer1 are present in the same complex in VSMCs and how Homer1 contributes to VSMC SOCs, proliferation, and migration leading to neointima formation. Homer1 expression levels are upregulated in balloon-injured vs. uninjured VSMCs. Coimmunoprecipitation assays revealed the presence and interaction of all SOC components in the injured VSMCs, where Homer1 interacts with Orai1 and various TRPC channels. Accordingly, knockdown of Homer1 in cultured VSMCs partially inhibited SOCs, VSMC migration, and VSMC proliferation. Neointimal area was reduced after treatment with an adeno-associated viral vector expressing a short hairpin RNA against Homer1 mRNA (AAV-shHomer1). These findings stress the role of multiple Ca 2+ influx channels in VSMCs and are the first to show the role of Homer proteins in VSMCs and its importance in neointima formation.

Mammalian hearing owes its remarkable sensitivity and frequency selectivity to a local mechanical feedback process within the cochlea. Cochlear outer hair cells (OHCs) function as the key elements in the feedback loop in which the fast somatic motility of OHCs is thought to be the source of cochlear amplification. An alternative view is that amplification arises from active hair-bundle movement, similar to that seen in nonmammalian hair cells. We measured voltage-evoked hair-bundle motions in the gerbil cochlea to determine if such movements were also present in mammalian OHCs. The OHCs showed bundle movement with peak responses of up to 830 nm. The movement was insensitive to manipulations that would normally block mechanotransduction in the stereocilia, and it was absent in neonatal OHCs and prestin-knockout OHCs. These findings suggest that the bundle movement originated in somatic motility and that somatic motility has a central role in cochlear amplification in mammals.