R-Type Voltage-Gated Ca²âº Channels in Cardiac and Neuronal Rhythmogenesis.

During the past decades, an increasing number of ion channel and transporter types have been identified acting together to produce cardiac and neuronal pacemaker action potentials. The basis of pacemaker activity was understood in more detail by using single-microelectrode recordings on cells isolated from pacemaker regions. Meanwhile, this powerful technique was complemented by computer modeling and recombinant technologies, including gene inactivation of ion channels and transporters, which may be involved in the generation of the electrical activity of pacemaker cells. Several genes of the voltage-gated Ca(2+) channel (VGCC) family have been ablated, and their role in cardiac and neuronal pacemaking is compared in the present summary, focusing on the role of murine R-type voltage-gated Ca(2+) channels encoded by cacna1e and expressing the ion conducting subunit Cav2.3.

Stress and psychiatric disorder in urban Rawalpindi. Community survey.

BACKGROUND: Recent studies in rural areas of Pakistan have yielded high prevalence rates of common mental disorders, especially among women. AIMS: To investigate emotional distress and common mental disorders in a poor urban district using the same survey method. METHOD: First-stage screening of a slum district of Rawalpindi used the Bradford Somatic Inventory. Psychiatric interviews were conducted with stratified samples using the ICD-10 research diagnostic criteria. RESULTS: On a conservative estimate, 25% of women and 10% of men suffered from anxiety and depressive disorders. Levels of emotional distress increased with age in both men and women. Women living in joint households reported more distress than those living in unitary families. Higher levels of education were associated with lower risk of common mental disorders, especially in younger women. Emotional distress was negatively correlated with socio-economic variables among women. CONCLUSIONS: This study found levels of emotional distress and psychiatric morbidity in a poor district of Rawalpindi to be less than half those in a nearby rural village in the Punjab, although rates in women were still double those in men. Possible explanations are that more healthy people migrate to the cities or that urban living is more conducive to good mental health in Pakistan.

CD4+ beta islet cell-reactive T cell clones that suppress autoimmune diabetes in nonobese diabetic mice.

We report the isolation of a panel of CD4+ T helper type 1 autoreactive T cell clones from the spleen of unprimed nonobese diabetic mice, a murine model of human insulin-dependent diabetes mellitus. The T cell clones express a diverse repertoire of T cell receptors, three of which recognize beta islet cell autoantigen(s). The islet cell-reactive T cell clones inhibit adoptive transfer of insulin-dependent diabetes mellitus and intraislet lymphocytic infiltration. The protective capacity of the T cell clones correlates with their ability to produce a novel immunoregulatory activity that potently inhibits in vitro allogeneic mixed lymphocyte reaction. The partially purified activity significantly inhibited the adoptive transfer of diabetes. Our work provides evidence in support of the existence of T helper type 1, CD4+ T cells reactive to beta islet cell autoantigens that have acquired a protective instead of a diabetogenic effector function. These T cells mediate their protective action in part by production of an immunoregulatory activity capable of down-regulating immune responses, and they are likely to represent a population of regulatory T cells that normally plays a role in maintaining peripheral tolerance.