Pressure‐induced depression of synaptic transmission in the cerebellar parallel fibre synapse involves suppression of presynaptic N‐type Ca²⁺ channels

Abstract

High pressure induces CNS hyperexcitability while markedly depressing synaptic transmitter release. We studied the effect of pressure (up to 10.1 MPa) on the parallel fibre (PF) synaptic response in biplanar cerebellar slices of adult guinea pigs. Pressure mildly reduced the PF volley amplitude and to a greater extent depressed the excitatory field postsynaptic potential (fPSP). The depression of the PF volley was noted even at supramaximal stimulus intensities, indicating an effect of pressure on the amplitude of the action potential in each axon. Low concentrations of TTX mimicked the effects of pressure on the PF volley without affecting the fPSP. Application omega-conotoxin GVIA (omega-CgTx) reduced the synaptic efficacy by 34.3+/-2.7%. However, in the presence of omega-CgTx the synaptic depression at pressure was significantly reduced. Reduced Ca2+ entry by application of Cd2+ or low [Ca2+]o did not have a similar influence on the effects of pressure. Application of omega-AGA IVA, omega-AGA TK and Funnel-web spider toxin did not affect the synaptic response in concentrations that usually block P-type Ca2+ channels, whilst the N/P/Q-type blocker omega-conotoxin MVIIC reduced the response to 52.7+/-5.0% indicating the involvement of Q-type channels and R-type channels in the non-N-type fraction of Ca2+ entry. The results demonstrate that N-type Ca2+ channels play a crucial role in the induction of PF synaptic depression at pressure. This finding suggests a coherent mechanism for the induction of CNS hyperexcitability at pressure.

Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures

“…The threshold pressure for HPNS is variable and affected by the rate of compression (18). Details regarding the cellular mechanism(s) underlying HPNS are unclear (114), but it appears that both synaptic (74,76,85,228,229) and intrinsic membrane properties are involved (72,73,191,192,216). Several excellent reviews on HPNS exist elsewhere (18,100,104,114).…”

“…At that time, making intracellular recordings of mammalian neurons proved to be technically challenging due to the comparatively small size of the neurons, inaccessibility of the tissue preparation and microelectrode once the pressure vessel was sealed, and the challenge of maintaining mechanical stability of the electrophysiological recording while "diving" and "surfacing" (191,192). Consequently, the majority of in vitro hyperbaric studies of the mCNS have selected more robust electrophysiological techniques, such as extracellular recording of evoked population spikes in the hippocampus (76,118,191,192,229), macropatch clamp recordings in the cerebellar cortex (72)(73)(74), and cervical nerve recordings of respiratory-related neural activity (197,198). Compared with intracellular recordings, extracellular recordings are easier to initiate once the chamber is sealed and to maintain during the ensuing compression and decompression periods.…”

Combination Therapies for Traumatic Brain Injury – Prospective Considerations

“…Fluid shear models induce cellular deformation with rotating fluid flow between two plates and are advantageous in that cells can be imaged during application of the fluid shear (LaPlaca and Thibault, 1997; Edwards et al, 2001;Serbest et al, 2005). In hydrostatic pressure models, cells or tissues are placed in a chamber which is pressurized, either with a transient pressure pulse (similar to a fluid percussion injury) or a tonic applied load (Panizzon et al, 1998;Etzion and Grossman, 2000;Panickar et al, 2002). Combined injury models have also been developed.…”

Pressure (≤4 ATA) increases membrane conductance and firing rate in the rat solitary complex

“…As in previous studies (9,16,17,19,(42)(43)(44)(45), helium was chosen as the compression medium to mimic hydrostatic pressure. All inert gases exert narcotic actions that are directly related to their lipid solubility (2,6,13).…”

“…Presently, onset of HPNS is what limits human performance at great depths while hyperbaric gas mixtures of oxygen and inert gases are breathed (13). Although the exact cellular mechanisms underlying HPNS are unknown, neurophysiological studies indicate that hyperbaric pressure increases excitability of the central nervous system (CNS) by changes in both synaptic (16,17,19,50) and intrinsic membrane properties (20, 21, 24, 25, 34, 41-43, 48, 49; also reviewed in 6,13,22,23,38). It is also clear that the effects of hyperbaric pressure on the CNS are due to the direct effects of increased hydrostatic pressure (i.e., pressure per se) and not to the effects of increased gas partial pressures (i.e., narcotic actions) (13).…”