Selective pressure modulation of synaptic voltage-dependent calcium channels-involvement in HPNS mechanism

Exposure to hyperbaric pressure (HP) exceeding 100 msw (1.1 MPa) is known to cause a constellation of motor and cognitive impairments named high-pressure neurological syndrome (HPNS), considered to be the result of synaptic transmission alteration. Long periods of repetitive HP exposure could be an occupational risk for professional deep-sea divers. Previous studies have indicated the modulation of presynaptic Ca2+ currents based on synaptic activity modified by HP. We have recently demonstrated that currents in genetically identified cellular voltage-dependent Ca2+ channels (VDCCs), Ca(V)1.2 and Ca(V)3.2 are selectively affected by HP. This work further elucidates the HPNS mechanism by examining HP effect on Ca2+ currents in neuronal VDCCs, Ca(V)2.2 and Ca(V)2.1, which are prevalent in presynaptic terminals, expressed in Xenopus oocytes. HP augmented the Ca(V)2.2 current amplitude, much less so in a channel variation containing an additional modulatory subunit, and had almost no effect on the Ca(V)2.1 currents. HP differentially affected the channels' kinetics. It is, therefore, suggested that HPNS signs and symptoms arise, at least in part, from pressure modulation of various VDCCs.