Single point mutations affect fatty acid block of human myocardial sodium channel α subunit Na+ channels

Suppression of cardiac voltage-gated Na+ currents is probably one of the important factors for the cardioprotective effects of the n-3 polyunsaturated fatty acids (PUFAs) against lethal arrhythmias. The α subunit of the human cardiac Na+ channel (hH1α) and its mutants were expressed in human embryonic kidney (HEK293t) cells. The effects of single amino acid point mutations on fatty acid-induced inhibition of the hH1α Na+ current (INa) were assessed. Eicosapentaenoic acid (EPA, C20:5n-3) significantly reduced INa in HEK293t cells expressing the wild type, Y1767K, and F1760K of hH1α Na+ channels. The inhibition was voltage and concentration-dependent with a significant hyperpolarizing shift of the steady state of INa. In contrast, the mutant N406K was significantly less sensitive to the inhibitory effect of EPA. The values of the shift at 1, 5, and 10 μM EPA were significantly smaller for N406K than for the wild type. Coexpression of the β1 subunit and N406K further decreased the inhibitory effects of EPA on INa in HEK293t cells. In addition, EPA produced a smaller hyperpolarizing shift of the V1/2 of the steady-state inactivation in HEK293t cells coexpressing the β1 subunit and N406K. These results demonstrate that substitution of asparagine with lysine at the site of 406 in the domain-1-segment-6 region (D1-S6) significantly decreased the inhibitory effect of PUFAs on INa, and coexpression with β1 decreased this effect even more. Therefore, asparagine at the 406 site in hH1α may be important for the inhibition by the PUFAs of cardiac voltage-gated Na+ currents, which play a significant role in the antiarrhythmic actions of PUFAs.

Induction of Acclimative Proteolysis of the Light-Harvesting Chlorophyll a/b Protein of Photosystem II in Response to Elevated Light Intensities1

Most plants have the ability to respond to fluctuations in light to minimize damage to the photosynthetic apparatus. A proteolytic activity has been discovered that is involved in the degradation of the major light-harvesting chlorophyll a/b-binding protein of photosystem II (LHCII) when the antenna size of photosystem II is reduced upon acclimation of plants from low to high light intensities. This ATP-dependent proteolytic activity is of the serine or cysteine type and is associated with the outer membrane surface of the stroma-exposed thylakoid regions. The identity of the protease is not known, but it does not correspond to the recently identified chloroplast ATP-dependent proteases Clp and FtsH, which are homologs to bacterial enzymes. The acclimative response shows a delay of 2 d after transfer of the leaves to high light. This lag period was shown to be attributed to expression or activation of the responsible protease. Furthermore, the LHCII degradation was found to be regulated at the substrate level. The degradation process involves lateral migration of LHCII from the appressed to the nonappressed thylakoid regions, which is the location for the responsible protease. Phosphorylated LHCII was found to be a poor substrate for degradation in comparison with the unphosphorylated form of the protein. The relationship between LHCII degradation and other regulatory proteolytic processes in the thylakoid membrane, such as D1-protein degradation, is discussed.

Zeitschrift für Pflanzenzüchtung.

3, 1915

Zeitschrift für Pflanzenzüchtung.

8, 1921-1922

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

3

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

8

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

10

Zeitschrift für Gärungsphysiologie.

3, 1913

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

22

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

7

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

9

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

6

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

17

Der Tropenpflanzer; zeitschrift für tropische landwirtschaft.

11