Abstract
Neurological research has traditionally emphasized neuronal components of the nervous system. Recent findings suggest, however, that astrocytes harbor greater (patho-)physiological significance than previously thought. Known to provide mechanical support and chemical control of the neuronal environment (neurotransmitter clearance, extracellular K+ siphoning, etc.), newer data now additionally tie astrocytes to pharmaceutical pathways (Nature 433:73) and neurological disorders such as epilepsy (Nat. Med. 11:973), calling for a clearer molecular description of astrocyte function. The inwardly-rectifying K+ channel Kir4.1 (KCNJ10) is exclusively expressed in astrocytes in the brain. Due to its central role in astroglial K+ buffering, Kir4.1 is likely a critical element of astrocyte performance. We examined the effects of various neuroactive and neurotoxic compounds on human Kir4.1 using heterologous expression and the whole-cell configuration of the patch-clamp technique and found that the antiarrhythmic/antimalarial agent quinidine reversibly blocked Kir4.1 current in a time-dependent manner at concentrations slightly above the therapeutic range. Voltages positive to the Nernstian potential strongly enhanced Kir4.1 block, but frequency and number of the supplied depolarizing pulses seemed to be of little importance. It is conceivable that electrochemical alterations caused by astroglial ion channel block are in fact responsible for numerous so-far unexplained neurological effects of commonly administered therapeutic agents. [J Physiol Sci. 2006;56 Suppl:S82]
