Altered Potassium Ion Homeostasis in Hearing Loss

Connexins, Kv-type ion channels, and pannexins have a dominant role in maintaining the potassium ion homeostasis in the cochlea. The cellular background currents are sustained by Kir2.1 ion channels; however, their involvement in the hearing system is less clear. In this study, the mutations of gap junction proteins beta 2 (GJB2), beta 3 (GJB3) and beta 6 (GJB6) were screened in the white Caucasian population in Hungary using gene mapping and immunofluorescence methods from translated proteins of these genes—connexins on blood cells. Expression of connexins and Kir2.1 ion channels was investigated in the blood cells of deaf patients prior to cochlear implantation, and the results show significantly decreased amounts of connexin26 and connexin43. In addition, the coexpression of Kir2.1 ion channels with synapse-associated 97 proteins was partially impaired. Our investigation revealed a reduced level of Kir2.1 channels in deaf patients indicating a crucial role for the functional Shaker superfamily of K+ channels in the non-diseased hearing system

Alternative stabilities of a proline-rich antibacterial peptide in vitro and in vivo

The proline-rich designer antibacterial peptide dimer A3-APO is currently under preclinical development for the treatment of systemic infections caused by antibiotic-resistant Gram-negative bacteria. The peptide showed remarkable stability in 25% mouse serum in vitro, exhibiting a half-life of ∼100 min as documented by reversed-phase chromatography. Indeed, after a 30-min incubation period in undiluted mouse serum ex vivo, mass spectrometry failed to identify any degradation product. The peptide was still a major peak in full blood ex vivo, however, with degradation products present corresponding to amino-terminal cleavage. When injected into mice intravenously, very little, if any unmodified peptide could be detected after 30 min. Nevertheless, the major early metabolite, a full single-chain fragment, was detectable until 90 min, and this fragment exhibited equal or slightly better activity in the broth microdilution antimicrobial assay against a panel of resistant Enterobactericeae strains. The Chex1-Arg20 metabolite, when administered three times at 20 mg/kg to mice infected with a sublethal dose (over LD50) of an extended spectrum β-lactamase-producing Escherichia coli strain, completely sterilized the mouse blood, similar to imipenem added at a higher dose. The longer and presumably more immunogenic prodrug A3-APO, injected subcutaneously twice over a 3-wk period, did not induce any antibody production, indicating the suitability of this peptide or its active metabolite for clinical development