Central sympathetic chemo sensitivity and Kir1 potassium channels in the cat

The possible involvement of potassium channels in central chemosensitivity, with special reference to the Kirl1 potassium channel, was investigated by studying the CO, 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,) or postganglionic (renal) sympathetic nerves after perfusion of the lower brainstem via the left vertebral artery with CO2-enriched saline solution. Unspecific K+ channel blockade by BaCl2 reduced the excitatory response of sympathetic activity after CO2-perfusion to 56% of control. A quantitatively similar inhibition of the central CO2 response was obtained after administration of 9-fluorenylmethylchloroformate (FMOC-Cl) which eliminates pH sensitivity of Kir1 and Kir4.1. Furthermore, two structurally different Kirl inhibiting toxins, tertiapin and Lq2, also reduced the central CO2 response to similar to50% of control. In contrast, charybdotoxin (CTX) had no effect on the CO2 response. Using RT-PCR the expression of mRNA homologous to rat Kirl mRNA was identified in the cat medulla oblongata. These data suggest that a modulation of potassium channel activity possibly via Kirl may contribute to central chemosensitivity. (C) 2002 Elsevier Science B.V. All rights reserved.