Altered Hippocampal Synaptic Potentiation in P2X₄Knock-Out Mice

Abstract

P2X 4 purinergic receptors are calcium-permeable, ATP-activated ion channels. In the CA1 area of the hippocampus, they are located at the subsynaptic membrane somewhat peripherally to AMPA receptors. The possible role of P2X 4 receptors has been difficult to elucidate because of the lack of selective antagonists. Here we report the generation of a P2X 4 receptor knock-out mouse and show that long-term potentiation (LTP) at Schaffer collateral synapses is reduced relative to that in wild-type mice. Ivermectin, which selectively potentiates currents at P2X 4 , was found to increase LTP in wild-type mice but had no effect in P2X 4 knock-out mice. We suggest that calcium entry through subsynaptic P2X 4 receptors during high-frequency stimulation contributes to synaptic strengthening.

Amino acid variations resulting in functional and nonfunctional zebrafish P2X1 and P2X5.1 receptors

“…The zebrafish family of P2X receptors is comprised of nine genes, one copy of P2X 1 , P2X 2 , and P2X 7 , and two paralogous copies of P2X 3 , P2X 4 , and P2X 5 . At this time there is no evidence for the existence of a gene encoding P2X 6 in the zebrafish genome.…”

“…Although mammals typically possess seven genes encoding P2X receptors, the partial duplication of the zebrafish genome has resulted in nine genes. The duplicated paralogs of P2X 3 and P2X 4 were originally designated as zP2X 3a , zP2X 3b , zP2X 4a , and zP2X 4b . However we will refer to these sequences as zP2X 3.1 , zP2X 3.2 , zP2X 4.1 , and zP2X 4.2 to distinguish them from the mammalian nomenclature for P2X receptors, which uses subscripted letters to indicate splice variants (as recommended by the guidelines established for zebrafish nomenclature, http://zfin.org/zf_info/nomen.html).…”

“…Another striking feature of both zP2X 2 variants was the sequence EMR at amino acid positions 70-72. In P2X [1][2][3][4][5][6][7] receptors from most other species, this site is occupied by a highly conserved KXK motif [17]. In human P2X 1 , rat P2X 2 , and rat P2X 4 , mutation of either of these two highly conserved lysines severely impaired ATP potency [20][21][22].…”

“…Although P2X receptors are widely expressed by both muscle and neural tissue in many organisms, only a handful of functions in these tissues have been attributed to members of this family. Most notably mouse knock outs have implicated P2X 1 in the neurogenic control of smooth muscle [2], P2X 2 and P2X 3 in nociception and as the post-synaptic receptors of neurons that receive input from taste cells [3], and P2X 4 in long-term potentiation [4]. These four examples represent the contribution of only four members of the family, in only a subset of cells known to express P2X receptors.…”

Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea

“…5 A-D). Because the P2X 4 receptor seems to be insensitive to purinergic blockers (17), we probed the spiking activity in IHCs from the P2X 4 knockout (KO) mice (18). The mean SR (control, 0.81 ± 0.1 Hz; P2X 4 KO, 0.99 ± 0.04 Hz), the CV from the interspike interval (control, 6.14 ± 0.68; P2X 4 KO, 8.86 ± 2.24), and the membrane potential (control, −60.41 ± 1.57 mV; P2X 4 KO, −60.55 ± 1.97 mV) were comparable between the genotypes, ruling out the involvement of the P2X 4 receptor in the AP firing ( Fig.…”