Calcium Flux Through Predominantly Independent Purinergic ATP and Nicotinic Acetylcholine Receptors

Abstract

Ligand-gated nicotinic acetylchoto serve as intracellular messengers that modulate ion chanline receptors (nAChRs) and purinergic ATP receptors are often nels and alter synaptic function (Fuchs and Morrow 1992; expressed in the same peripheral and central neurons, and ATP and Gray et al. 1996;McGehee et al. 1995;Vernino et al. 1992). acetylcholine (ACh) are stored together in some synaptic vesicles.Although permeability ratios of Ca 2/ to Na / have been Evidence has suggested that nAChRs and ATP receptors are not measured many times, those measurements do not have a independent and that some agonists strongly cross-activate and strong theoretical basis for accurately predicting the Ca 2/ desensitize both receptor types. Rat sympathetic neurons and nAChRs expressed in Xenopus oocytes were studied to determine flux through the channels (see Hille 1975; Vernino et al. the significance of the interactions caused by the two agonist types. 1994). Permeability ratios are calculated from the Goldman-Current amplitudes induced with separate or combined applications Hodgkin-Katz equations, but those equations do not comof ATP and nicotine are ú90% additive and independent. Half of pletely describe ion permeation in biological channels. all neurons tested responded to either ATP or nicotine but not to Therefore we measured the quantitative Ca 2/ flux through both, indicating differences in the expression of the two receptors. ATP-and acetylcholine (ACh)-activated channels to pro-In neurons that expressed both receptor types, the nAChRs were vide an accurate value for predicting activity-dependent ininhibited by the activity-dependent open-channel blocker chlori-1407

An Angstrom Scale Interaction between Plasma Membrane ATP-Gated P2X2and α4β2Nicotinic Channels Measured with Fluorescence Resonance Energy Transfer and Total Internal Reflection Fluorescence Microscopy

“…Data for dendrites followed a similar pattern: we measured strong FRET for dendritic P2X 2 -C/P2X 2 -Y and ␣ 4 -Y/␤ 2 -C channels at 36 Ϯ 5% (n ϭ 7) and 27 Ϯ 4% (n ϭ 4), but 0% FRET for dendritic P2X 2 -C and ␣ 4 /␤ 2 -Y channels (n ϭ 7). The FRET differences between hippocampal and midbrain neurons extend previous functional studies suggesting that interactions between P2X and nicotinic channels may vary depending on the neuron type (Nakazawa, 1994;Rogers et al, 1997).…”

“…Interestingly, we found robust FRET between P2X 2 and ␣ 4 ␤ 2 channels in hippocampal neurons but not in midbrain neurons. Neuron-specific interactions also occur in the periphery: crossinhibition occurred in sympathetic neurons from the celiac ganglion but not in those from the superior cervical ganglion (Rogers et al, 1997). Perhaps there are neuron-specific cues that govern cross-inhibition, for example variable expression of interacting or targeting proteins.…”

Hyperpolarization‐activated cationic currents (Ih) in neurones of the trigeminal mesencephalic nucleus of the rat

“…It is interesting to note, however, that both áµ adrenoceptors and NK1 receptors couple to G proteins, and their activation can result in the elevation of intracellular calcium levels (Aantaa et al 1995;Khawaja & Rogers, 1996). P2X receptor channels are calcium permeable and would also be expected to increase intracellular calcium levels (Rogers & Dani, 1995;Rogers et al 1997). In future work it will be interesting to determine the mechanism(s) by which Ih can be modulated by calcium either released from intracellular stores or entering from the cell exterior, or possibly by a secondary calcium-dependent process.…”

Molecular Physiology of P2X Receptors

“…In rat superior cervical ganglion cells, ATP evokes inward currents (73,233,324,327,386,387) and elicits the release of norepinephrine (30,487). Rogers and Dani (387) measured directly the calcium permeability of the P2X receptors by simultaneous measurements of intracellular calcium and membrane currents.…”