Changes in ionic currents of respiratory neurons produce sympathetic overactivity in chronic intermittent hypoxic rats

Abstract

The coupling between respiratory and sympathetic neuronal activities is enhanced in rats submitted to chronic intermittent hypoxia (CIH) and contributes to the development of hypertension in this experimental model. We evaluated the mechanisms involved in the CIH‐induced changes in electrophysiological properties of medullary respiratory and pre‐sympathetic neurons. One day after the protocol of 10 days of CIH, using an in situ preparation we performed simultaneous recordings of respiratory and sympathetic nerves with blind whole cell path‐clamp of respiratory and pre‐sympathetic neurons of ventrolateral medulla. In CIH rats, the increased firing frequency of pre‐sympathetic neurons (n=27) and thoracic sympathetic activity (n=30), time‐locked with abdominal late‐expiratory activity (n=25), were dependent of synaptic inputs from respiratory neurons. Since medullary post‐ and pre‐inspiratory (pre‐I) neurons modulate the firing frequency of pre‐sympathetic neurons, we observed that the decreased and increased of intrinsic firing frequency of post‐I (n=28) and pre‐I neurons (n=28), respectively, were accompanied by changes in their input resistance and rheobase after CIH. These changes were due to increase in the inward riluzole‐sensitive persistent sodium current (iNaP; n=6) in pre‐I neurons and in the 4‐aminopyridine‐sensitive component of transient outward potassium current (TOC; n=9) in the post‐I neurons after CIH. These data describe the mechanisms underlying sympathetic overactivity, which critically depend on changes of ionic currents of medullary respiratory neurons of CIH rats.Support:FAPESP, CAPES and CNPQ.