Central sympathetic chemosensitivity and Kir1 potassium channels in the cat.
The possible involvement of potassium channels in central chemosensitivity, with special reference to the Kir1.1 potassium channel, was investigated by studying the CO(2) response of presympathetic neurons in the rostroventrolateral medulla (RVLM) in the absence or presence of various K(+) channel inhibitors. Synaptic input to RVLM neurons was blocked by local injection of omega-agatoxin and omega-conotoxin. Activity of RVLM neurons was measured by recording the electrical activity in preganglionic (WR-T(3)) or postganglionic (renal) sympathetic nerves after perfusion of the lower brainstem via the left vertebral artery with CO(2)-enriched saline solution. Unspecific K(+) channel blockade by BaCl(2) reduced the excitatory response of sympathetic activity after CO(2)-perfusion to 56% of control. A quantitatively similar inhibition of the central CO(2) response was obtained after administration of 9-fluorenylmethylchloroformate (FMOC-Cl) which eliminates pH sensitivity of Kir1 and Kir4.1. Furthermore, two structurally different Kir1 inhibiting toxins, tertiapin and Lq2, also reduced the central CO(2) response to approximately 50% of control. In contrast, charybdotoxin (CTX) had no effect on the CO(2) response. Using RT-PCR the expression of mRNA homologous to rat Kir1 mRNA was identified in the cat medulla oblongata. These data suggest that a modulation of potassium channel activity possibly via Kir1 may contribute to central chemosensitivity.
Schultz
Jobst Hendrik
JH
Institut für Vegetative Physiologie und Pathophysiologie, Universität Hamburg, D-20246, Hamburg, Germany.
Czachurski
Jürgen
J
Volk
Tilmann
T
Ehmke
Heimo
H
Seller
Horst
H
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000187:drug effects*
C510692:Kcnj1 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D002245:Carbon Dioxide