Regulation of Neurotransmitter Release by K+ Channels.

K+ channels play potent roles in the process of neurotransmitter release by influencing the action potential waveform and modulating neuronal excitability and release probability. These diverse effects of K+ channel activation are ensured by the wide variety of K+ channel genes and their differential expression in different cell types. Accordingly, a variety of K+ channels have been implicated in regulating neurotransmitter release, including the Ca2+- and voltage-gated K+ channel Slo1 (also known as BK channel), voltage-gated K+ channels of the Kv3 (Shaw-type), Kv1 (Shaker-type), and Kv7 (KCNQ) families, G-protein-gated inwardly rectifying K+ (GIRK) channels, and SLO-2 (a Ca2+-. Cl-, and voltage-gated K+ channel in C. elegans). These channels vary in their expression patterns, subcellular localization, and biophysical properties. Their roles in neurotransmitter release may also vary depending on the synapse and physiological or experimental conditions. This chapter summarizes key findings about the roles of K+ channels in regulating neurotransmitter release.

New substitutions on NS1 protein from influenza A (H1N1) virus: Bioinformatics analyses of Indian strains isolated from 2009 to 2020.

Background and Aims: Nonstructural (NS1) protein is mainly involved in virulence and replication of several viruses, including influenza virus A (H1N1); surveillance of the latter started in India in 2009. The objective of this study was to identify the new substitutions in NS1 protein from the influenza virus A (H1N1) pandemic 2009 (pdm09) strain isolated in India. Methods: The sequences of NS1 proteins from influenza A(H1N1) pdm09 strains isolated in India were obtained from publicly available databases. Multiple sequence alignment and phylogeny analyses were performed to confirm the "consistent substitutions" on NS1 protein from H1N1 (pdm09) Indian strains. Here, "consistent substitutions" were defined as the substitutions observed in all the sequences isolated in a year. Comparative analyses were performed among NS1 Indian sequences from A(H1N1) pdm09, A (H1N1) seasonal and A(H3N2) strains, and from A (H1N1) pdm09 global strains. Results: Eight substitutions were identified in the NS1 Indian sequence from the A(H1N1) pdm09 strain, two in RBD, five in ED, and one in the linker region. Three new substitutions were reported in this study at NS1 sequence positions 2, 80, and 155, which evolved within 2015-2019 and became "consistent." These new substitutions were associated with conservative paired substitutions in the alternative domains of the NS1 protein. Three paired substitutions were (i) D2E and E125D, (ii) T80A and A155T, and (iii) E55K and K131E. Conclusions: This study indicates the continuous evolution of NS1 protein from the influenza A virus. The new substitutions at positions 2 and 80 occurred in the RNA binding and eIF4GI binding domains. The D2E substitution evolved simultaneously with the E125D substitution that involved viral replication. The third new substitution at position 155 occurred in the PI3K binding domain. The possible consequences of these substitutions on host-pathogen interactions are subject to further experimental and computational verification.