Elevated potassium elicits recurrent surges of large GABA_A-receptor-mediated post-synaptic currents in hippocampal CA3 pyramidal neurons

Abstract

Previously, we found that rat hippocampal CA3 interneurons become hyperactive with increasing concentrations of extracellular K(+) up to 10 mM. However, it is unclear how this enhanced interneuronal activity affects pyramidal neurons. Here we voltage-clamped rat hippocampal CA3 pyramidal neurons in vitro at 0 mV to isolate γ-aminobutyric acid (GABA)-activated inhibitory post-synaptic currents (IPSCs) and measured these in artificial cerebrospinal fluid (aCSF) and with 10 mM K(+) bath perfusion. In aCSF, small IPSCs were present with amplitudes of 0.053 ± 0.007 nA and a frequency of 0.27 ± 0.14 Hz. With 10 mM K(+) perfusion, IPSCs increased greatly in frequency and amplitude, culminating in surge events with peak amplitudes of 0.56 ± 0.08 nA, that appeared and disappeared cyclically with durations lasting 2.02 ± 0.37 min repeatedly, up to 10 times over a 30-min bath perfusion of elevated K(+). These large IPSCs were GABA(A)-receptor mediated and did not involve significant desensitization of this receptor. Perfusion of a GABA transporter inhibitor (NO-711), glutamate receptor inhibitors CNQX and APV, or a gap junctional blocker (carbenoxolone) prevented the resurgence of large IPSCs. Pressure ejected sucrose resulted in the abolishment of subsequent surges. No elevated K(+)-mediated surges were observed in CA3 interneurons from the stratum oriens layer. In conclusion, these cyclic large IPSC events observable in CA3 pyramidal neurons in 10 mM KCl may be due to transient GABA depletion from continuously active interneuronal afferents.

Excitation and inhibition in recurrent networks mediate collision avoidance in Xenopus tadpoles

“…In one series of experiments we used ACSF with elevated potassium concentrations ([K + ] out = 7 m m , compared with 4 m m in control) to increase the resting membrane potential of cells in the brain. The subthreshold depolarisation of neurons promotes spontaneous spiking (Shin et al ., ) and the spontaneous release of neurotransmitters from presynaptic terminals (Jensen et al ., ; Shin et al ., ), but also facilitates the inactivation of voltage‐gated Na channels, suppressing burst generation (Pratt & Aizenman, ; Remy et al ., ; Tsuruyama et al ., ). We found that, in ACSF with elevated [K + ] out , bursting was suppressed, and OT cells fired fewer spikes in response to visual stimulation (Fig.…”

Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ‐aminobutyric acid type B receptor activity

“…These same interneurons may be the source of the endogenous GABA tone seen in the “No Mg/High K” model, which could explain why WIN could not decrease GABA release enough to attenuate presynaptic GABA B receptor activation. Interestingly, elevated extracellular potassium alone has been shown to trigger increased release of GABA from hippocampal interneurons (Shin et al 2011) which could result in GABA B receptor activation and decreased WIN sensitivity. Our finding that the “High K” model was equally sensitive to WIN suggests that only the combination of elevated potassium and omission of magnesium generates sufficient GABA B activity to interfere with the actions of WIN.…”

Transition to Seizure: Ictal Discharge Is Preceded by Exhausted Presynaptic GABA Release in the Hippocampal CA3 Region

“…A number of factors can lead to a decrease in presynaptic release including decreased interneuronal activity resulting in fewer action potentials invading the nerve terminals as discussed above, impaired Ca 2ϩ entry, modulation of release of GABA by activation of presynaptic GABA B receptors (Peet and McLennan, 1986) or presynaptic glutamate receptors (Stafford et al, 2010), and exhaustion of GABA vesicles (Shin et al, 2011). A technique for releasing neurotransmitter has been described using sucrose application (Rosenmund and Stevens, 1996) that releases the same pool of vesicles available for Ca 2ϩ -dependent release by a Ca 2ϩ -independent mechanism.…”