Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration.

Unlabelled: Several reports suggest that clinically used concentrations of inhaled anesthetics can increase conductance through noninactivating potassium channels and that the resulting hyperpolarization might decrease excitability, thereby leading to the anesthetic state. We speculated that animals deficient in such potassium channels might be resistant to the effects of anesthetics. Thus, in the present study, we measured the minimum alveolar anesthetic concentration (MAC) needed to prevent movement in response to a noxious stimulus in 50% of adult mice lacking functional KCNK5 potassium channel subunits and compared these results with those for heterozygous and wild-type mice.

Specificity of human and rat orthologs of the concentrative nucleoside transporter, SPNT.

To understand the roles that nucleoside transporters play in the in vivo distribution of clinically important nucleoside analogs, the substrate specificity of each transporter isoform should be determined. In the present work, we studied the substrate specificities of the human and rat orthologs of the Na+-dependent purine-selective nucleoside transporter (SPNT; concentrative nucleoside transporter 2), for nucleosides, nucleobases, and base- and ribose-modified nucleoside analogs. The two-electrode voltage-clamp technique in Xenopus laevis oocytes expressing these transporters was used.

Molecular cloning of a Na+-dependent nucleoside transporter from rabbit intestine.

Purpose: Substantial species differences in the transport kinetics of nucleosides and therapeutic nucleoside analogs have been observed in various experimental systems. To explain these differences at a molecular level, it is necessary to clone the relevant transporters and examine their functional characteristics in heterologous expression systems. The goal of the present study was to clone the nucleoside transporters present in rabbit, an important preclinical animal model, and to functionally characterize the clone(s).

Electrophysiological analysis of the substrate selectivity of a sodium-coupled nucleoside transporter (rCNT1) expressed in Xenopus laevis oocytes.

Nucleoside transporters that mediate cellular uptake of therapeutic nucleoside analogs are major determinants of the pharmacokinetic properties of these compounds. Understanding the substrate selectivity of these transporters is critical in the development of therapeutic nucleoside analogs with optimal pharmacokinetic properties, including high oral bioavailability and tissue-specific distribution. In general, substrate selectivity of nucleoside transporters has been evaluated indirectly by inhibition studies.

Mechanisms of transport of nucleosides and nucleoside analogues in choroid plexus.

Nucleoside and nucleobase analogues are being used to treat a number of viral infections of the central nervous system (CNS) including herpes-simplex encephalitis, cytomegalovirus retinitis, and AIDS-related dementia complex. Delivery of nucleoside analogues to the CNS is considered a key challenge in the treatment of these diseases. In this review, we focus on the mechanisms of transport of nucleosides and nucleoside analogues in the choroid plexus.