Inhibitory Decrease Research Articles

Protofibrillar Amyloid Beta Modulation of Recombinant hCaV2.2 (N-Type) Voltage-Gated Channels.

Cav2.2 channels are key regulators of presynaptic Ca2+ influx and their dysfunction and/or aberrant regulation has been implicated in many disease states; however, the nature of their involvement in Alzheimer's disease (AD) is less clear. In this short communication, we show that recombinant hCav2.2/b1b/a2d1 channels are modulated by human synthetic AD-related protofibrillar amyloid beta Ab1-42 peptides. Structural studies revealed a time-dependent increase in protofibril length, with the majority of protofibrils less than 100 nm at 24 h, while at 48 h, the majority were longer than 100 nm. Cav2.2 modulation by Ab1-42 was different between a 'low' (100 nM) and 'high' (1 µM) concentration in terms of distinct effects on individual biophysical parameters. A concentration of 100 nM Ab1-42 caused no significant changes in the measured biophysical properties of Cav2.2 currents. In contrast, 1 µM Ab1-42 caused an inhibitory decrease in the current density (pA/pF) and maximum conductance (Gmax), and a depolarizing shift in the slope factor (k). These data highlight a differential modulation of Cav2.2 channels by the Ab1-42 peptide. Discrete changes in the presynaptic Ca2+ flux have been reported to occur at an early stage of AD; therefore, this study reveals a potential mechanistic link between amyloid accumulation and Cav2.2 channel modulation.

Stepwise adaptation to salinity in the green alga Nannochloris bacillaris

A severe inhibitory decrease in water potential owing to salinity increase (ψ = −0.2 to −5.5 MPa) was tolerated in Nannochloris bacillaris Naumann if an intermediate salinity step at ψ = −2.6 MPa was provided. Photosynthesis, respiration, and growth were all enhanced by the provision of an intermediate step. The length of time of the application of the intermediate salinity step was critical to the resulting abilities of the cells to exhibit substantial adaptation. Increasing the length of the intermediate step from 10 to 120 min resulted in a 168-fold increase in the rate of photoassimilation of bicarbonate. Adaptation of other functions (e.g., growth) took much longer. The effects of pulse shocks, downward then upward water potentials, indicated that when there was an inhibition of photosynthesis and it was irreversible over the short term. Pulse shocks to noninhibitory water potentials did not cause inhibition. These results were correlated with measurements of volume changes, rates of excretion of solutes, and ultrastructural changes.