The roles of the subunits in the function of the calcium channel

Dihydropyridine-sensitive voltage-dependent L-type calcium channels are critical to excitation-secretion and excitation-contraction coupling. The channel molecule is a complex of the main, pore-forming subunit alpha 1 and four additional subunits: alpha 2, delta, beta, and gamma (alpha 2 and delta are encoded by a single messenger RNA). The alpha 1 subunit messenger RNA alone directs expression of functional calcium channels in Xenopus oocytes, and coexpression of the alpha 2/delta and beta subunits enhances the amplitude of the current. The alpha 2, delta, and gamma subunits also have pronounced effects on its macroscopic characteristics, such as kinetics, voltage dependence of activation and inactivation, and enhancement by a dihydropyridine agonist. In some cases, specific modulatory functions can be assigned to individual subunits, whereas in other cases the different subunits appear to act in concert to modulate the properties of the channel

Comparação do equilíbrio postural de idosos sedentários, praticantes de diferentes modalidades de exercícios e adultos jovens

O objetivo deste estudo foi comparar o equilíbrio postural de idosos praticantes de duas modalidades de exercícios físicos, idosos não praticantes e adultos jovens, na presença e ausência de informação visual. Participaram 51 indivíduos (n = 31 do sexo feminino e n = 20 do sexo masculino), subdivididos em quatro grupos: idosos praticantes de karatê (GIKA, n = 11), idosos praticantes de ginástica generalizada (GIGG, n = 16), idosos não praticantes de exercícios físicos (GINP, n = 12), e um grupo controle de adultos jovens (GAJ, n = 12). A tarefa constituiu em permanecer em apoio estático, posição semi tandem, sobre a plataforma de força por 40 segundos. Duas condições experimentais foram realizadas: com visão e sem visão. As variáveis de controle postural obtidas a partir do centro de pressão (Cop) foram: área de oscilação do Cop, velocidade e amplitude média de oscilação do Cop nas direções ântero-posterior e médio-lateral. Os resultados indicaram que os idosos praticantes de exercícios físicos GIKA e GIGG obtiveram desempenhos semelhantes, não diferenciando a modalidade praticada, tanto na condição com visão quanto sem visão, aproximando seu desempenho de adultos jovens, mais especificamente o grupo GIGG. Na condição sem visão, todos os grupos mostraram-se mais suscetíveis à instabilidade postural. O grupo GINP apresentou maior oscilação postural em todas as variáveis analisadas quando comparado aos outros grupos, apresentando maiores diferenças com o grupo GIGG e GAJ. Sendo assim, os grupos de idosos praticantes não se diferenciaram, se aproximando ao desempenho dos adultos jovens. Compreende-se que a prática de exercícios físicos tem papel importante e eficaz na manutenção do equilíbrio postural durante o envelhecimento e pode evitar possíveis quedas

Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity.

Kv7.4 channels are key determinants of arterial contractility and cochlear mechanosensation that, like all Kv7 channels, have an obligatory requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). βγ G proteins (Gβγ) have been identified as novel positive regulators of Kv7.4. The present study ascertained whether Gβγ increased Kv7.4 open probability through an increased sensitivity to PIP2. In HEK cells stably expressing Kv7.4, PIP2 or Gβγ increased open probability in a concentration dependent manner. Depleting PIP2 prevented any Gβγ-mediated stimulation whilst an array of Gβγ inhibitors prohibited any PIP2-induced current enhancement. A combination of PIP2 and Gβγ at sub-efficacious concentrations increased channel open probability considerably. The stimulatory effects of three Kv7.2-7.5 channel activators were also lost by PIP2 depletion or Gβγ inhibitors. This study alters substantially our understanding of the fundamental processes that dictate Kv7.4 activity, revealing a more complex and subtle paradigm where the reliance on local phosphoinositide is dictated by interaction with Gβγ

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways

The communicative functions of metaphors between explanation and persuasion

In the literature, the pragmatic dimension of metaphors has been clearly acknowledged. Metaphors are regarded as having different possible uses, and in particular, they are commonly viewed as instruments for pursuing persuasion. However, an analysis of the specific conversational purposes that they can be aimed at achieving in a dialogue and their adequacy thereto is still missing. In this paper, we will address this issue focusing on the distinction between the explanatory and persuasive goal. The difference between explanation and persuasion is often blurred and controversial from a theoretical point of view. Building on the analysis of explanation in different theories and fields of study, we show how it can be conceived as characterized by a cognitive and a pragmatic dimension, where the transference of understanding is used pragmatically for different dialogical goals. This theoretical proposal will be applied to examples drawn from the medical context, to show how a pragmatic approach to explanation can account for the complexity of the cases that can be found in actual dialogical contexts