The effects of entry on incumbent innovation and productivity

How does firm entry affect innovation incentives in incumbent firms? Microdata suggest that there is heterogeneity across industries. Specifically, incumbent productivity growth and patenting is positively correlated with lagged greenfield foreign firm entry in technologically advanced industries, but not in laggard industries. In this paper we provide evidence that these correlations arise from a causal effect predicted by Schumpeterian growth theory—the threat of technologically advanced entry spurs innovation incentives in sectors close to the technology frontier, where successful innovation allows incumbents to survive the threat, but discourages innovation in laggard sectors, where the threat reduces incumbents' expected rents from innovating. We find that the empirical patterns hold using rich micro panel data for the United Kingdom. We control for the endogeneity of entry by exploiting major European and U.K. policy reforms, and allow for endogeneity of additional factors. We complement the analysis for foreign entry with evidence for domestic entry and entry through imports

A Novel Mechanism for Calmodulin Dependent Inactivation of Transient Receptor Potential Vanilloid 6

The paralogues TRPV5 and TRPV6 belong to the vanilloid subfamily of the Transient Receptor Potential (TRP) superfamily of ion channels and both play an important role in overall Cahomeostasis. The functioning of the channels centres on a tightly controlled Ca-dependent feedback mechanism where the direct binding of the universal Ca-binding protein calmodulin (CaM) to the channel's C-terminal tail is required for channel inactivation. We have investigated this interaction at the atomic level and propose that under basal cellular [CaCaM is constitutively bound to the channel's C-tail via CaM C-lobe only contacts. When cytosolic [Ca] increases charging the apo CaM N-lobe with Ca, the CaM:TRPV6 complex rearranges and the TRPV6 C-tail further engages the CaM N-lobe via a crucial interaction involving L707. In a cellular context, mutation of L707 significantly increased the rate of channel inactivation. Finally, we present a model for TRPV6 CaM-dependent inactivation, which involves a novel so-called "two-tail" mechanism whereby CaM bridges between two TRPV6 monomers resulting in closure of the channel pore

Atrial-ventricular differences in rabbit cardiac voltage-gated Na + currents: Basis for atrial-selective block by ranolazine

BACKGROUND Class 1 antiarrhythmic drugs are highly effective in restoring and maintaining sinus rhythm in atrial fibrillation patients but carry a risk of ventricular tachyarrhythmia. The anti-anginal agent, ranolazine, is a prototypic atrial-selective voltage-gated Na+ channel blocker but the mechanisms underlying its atrial-selective action remain unclear. OBJECTIVE The present study examined the mechanisms underlying the atrial-selective action of ranolazine. METHODS Whole-cell voltage-gated Na+ currents (INa) were recorded at room temperature (~22 °C) from rabbit isolated left atrial and right ventricular myocytes. RESULTS INa conductance density was ~1.8-fold greater in atrial than in ventricular cells. Atrial INa was activated at command potentials ~7 mV more negative and inactivated at conditioning potentials ~11 mV more negative than ventricular INa. The onset of inactivation of INa was faster in atrial cells than in ventricular myocytes. Ranolazine (30 μM) inhibited INa in atrial and ventricular myocytes in a use-dependent manner consistent with preferential activated/inactivated state block. Ranolazine caused a significantly greater negative shift in voltage of half-maximal inactivation in atrial cells than in ventricular cells, the recovery from inactivation of INa was slowed by ranolazine to a greater extent in atrial myocytes than in ventricular cells and ranolazine produced an instantaneous block that showed marked voltage-dependence in atrial cells. CONCLUSIONS Differences exist between rabbit atrial and ventricular myocytes in the biophysical properties of INa. The more negative voltage-dependence of INa activation and inactivation, together with trapping of the drug in the inactivated channel, underlies an atrial-selective action of ranolazine. <br/