Increases in N‐type calcium current augment transmitter release following three days of chronic intermittent hypoxia

Abstract

We previously reported changes in synaptic transmission between chemosensory afferent fibers and secondary neurons in NTS in response to chronic intermittent hypoxia (CIH). Ten days (10D) of CIH in rats produces an increase in the frequency of spontaneous miniature release of transmitter (mEPSC) while the evoked EPSC (eEPSC) is significantly reduced (Kline et al., J. Neurosci. 27:4663, 2007). We attributed the latter to a homeostatic response to the increased mEPSC and postulated that the two responses could be separated in time. Here we compared the eEPSC amplitude in rats subjected to a shorter hypoxic exposure, 3 days CIH with NORM and also compared mEPSC frequency in both groups. After 3D CIH, eEPSC amplitude was slightly elevated, 202±26 vs 182±4 pA. To the contrary, mEPSC release had already increased, 11± 3 (CIH) versus 5±1Hz (NORM) similar to values at 10D CIH (11.7±2.6 Hz). To address mechanisms, in voltage clamp studies we recorded calcium currents from soma of the presynaptic neurons. We compared the amplitude of N‐type calcium current (ω‐conotoxin GVIA‐sensitive) responsible for evoked release in cells isolated from 3D CIH or NORM rats. The current was increased (p<.02) after CIH (65±6 pA/pF) compared to control (42±7 pA/pF) suggesting that an increased functional expression of the N‐type channel may be responsible for the increase in spontaneous release as well as the small increase in evoked release at 3D CIH. HL090886