Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias.

Cardiac electrical activity is governed by different ion channels that generate action potentials. Acquired or inherited abnormalities in the expression and/or function of ion channels usually result in electrophysiological changes that can cause cardiac arrhythmias. Transcription factors (TFs) control gene transcription by binding to specific DNA sequences adjacent to target genes. Linkage analysis, candidate-gene screening within families, and genome-wide association studies have linked rare and common genetic variants in the genes encoding TFs with genetically-determined cardiac arrhythmias. Besides its critical role in cardiac development, recent data demonstrated that they control cardiac electrical activity through the direct regulation of the expression and function of cardiac ion channels in adult hearts. This narrative review summarizes some studies showing functional data on regulation of the main human atrial and ventricular Na+, Ca2+, and K+ channels by cardiac TFs such as Pitx2c, Tbx20, Tbx5, Zfhx3, among others. The results have improved our understanding of the mechanisms regulating cardiac electrical activity and may open new avenues for therapeutic interventions in cardiac acquired or inherited arrhythmias through the identification of TFs as potential drug targets. Even though TFs have for a long time been considered as 'undruggable' targets, advances in structural biology have led to the identification of unique pockets in TFs amenable to be targeted with small-molecule drugs or peptides that are emerging as novel therapeutic drugs.

Aseptic meningitis due to varicella-zoster virus: serum antibody levels and local synthesis of specific IgG, IgM, and IgA.

We used an indirect enzyme immunoassay to describe the evolution of serum levels and the intrathecal production of IgG, IgA, and IgM antibodies to varicella-zoster virus (VZV) in eight patients with a syndrome of acute aseptic meningitis (AAM) and evidence of intrathecal production of VZV-specific IgG antibodies. Four of the eight patients showed no cutaneous zoster while hospitalized. Our results suggested an etiologic relation between VZV and AAM in all cases. Furthermore, we observed some differences in the pattern of evolution of antibodies in serum and cerebrospinal fluid in relation to the presence or absence of cutaneous lesions in our patients. These differences could reflect different pathogenic mechanisms in the spread of VZV to the central nervous system and in the production of the AAM syndrome.

Intrathecal synthesis of IgG antibodies to varicella-zoster virus in two cases of acute aseptic meningitis syndrome with no cutaneous lesions.

IgG antibodies to varicella-zoster virus (VZV) were detected by indirect enzyme-immunoassay (EIA) in CSF of two patients with acute aseptic meningitis syndrome (AAMS) not associated with evident cutaneous lesion or recent history of zoster infection. Their characteristic features and serological data are compared with those observed in two patients with AAMS and zoster cutaneous lesions, and in 13 patients with AAMS of unknown or other etiology. According to several indexes applied to assess the origin of the detected antibodies, it is concluded that VZV IgG antibodies are of intrathecal production. The possible etiologic relationship between the neurological syndrome and the detection of VZV antibodies in CSF is discussed. Routine serological procedures are proposed for the diagnosis of CNS acute infections of probable viral etiology that should provide additional data on these rarely described cases.