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Query: UNIPROT:P46098 (
5-HT3 receptor
)
2,290
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mouse neuroblastoma cells of the clone N1E-115 express a variety of ion channels and receptors, including a number that is also involved in neurotransmission. Effects of
Pb2+
on several of these ion channels have been investigated under experimental conditions that allow electrophysiological recording of membrane current carried by distinct types of ion channels. In whole-cell voltage clamp experiments voltage-dependent calcium channels are blocked by
Pb2+
at micromolar concentrations, while voltage-dependent sodium channels are not affected by
Pb2+
. The neuronal type nicotinic acetylcholine (ACh) receptor-ion channel complex is sensitive to low concentrations of
Pb2+
. At 1 nM-3 microM,
Pb2+
reduces the peak amplitude of the ACh-induced inward current to 74%-10% of the control value in a concentration-dependent manner. However, at
Pb2+
concentration between 10 and 100 microM this blocking effect is reduced and kinetics of decay of the ACh-induced inward current are slowed. The effects of
Pb2+
on the nicotinic receptor-mediated inward current amplitude can be described by the sum of two sigmoidal concentration-effect curves with an IC50 value of 19 nM and an EC50 of 21 microM. The
serotonin 5-HT3 receptor
-ion channel complex is less sensitive to
Pb2+
. The serotonin-induced inward current is blocked by
Pb2+
with an IC50 value of 49 microM. In single channel patch clamp experiments internal
Pb2+
causes activation of calcium-activated potassium channels in N1E-115 cells. The two types of calcium-activated potassium channels show differential sensitivity: the low conductance (SK) channel is more sensitive to
Pb2+
than the high conductance (BK) channel. At micromolar concentrations
Pb2+
also induces an ion current mediated by metal ion-activated ion channels. Opening of these channels, which have a single channel conductance of 24 pS and a reversal potential of 0 mV, depends on
Pb2+
concentration. These effects of
Pb2+
support the hypothesis that
Pb2+
affects synaptic transmission by blocking presynaptic voltage-dependent calcium channels. On the other hand, effects on other sensitive target sites, the neuronal nicotinic ACh receptor in particular, clearly indicate that other targets may be involved in the toxic effects of
Pb2+
on the nervous system.
...
PMID:Differential neurotoxicological effects of lead on voltage-dependent and receptor-operated ion channels. 750 28
The effects of several metals on the serotonin receptor-channel complex were studied using mouse neuroblastoma N1E-115 cells which are known to be endowed with the 5-HT3 subclass of the receptor. The whole-cell patch clamp technique was used to record currents induced by serotonin at a concentration of 3 microM which was equivalent to the apparent dissociation constant. Methylmercury and mercuric chloride suppressed serotonin-induced currents irreversibly, with a 50% suppression being observed at concentrations of 3 microM and 2 microM, respectively.
Lead
and zinc suppressed the current with IC50S of 80 microM and 50 microM, respectively, and the effects of both metals were reversible after washing with metal-free solution. Lanthanum also suppressed the current with an IC50 of 10 microM, and the effect was partially reversible. Cadmium and cobalt augmented serotonin-induced currents slightly but consistently at a concentration of 100 microM, and the effect was reversible. Aluminum at 100 microM, had no effect on serotonin-induced currents. It was concluded that the
5-HT3 receptor
is endowed with a unique property with respect to the actions of metals which is not shared by some other ligand-gated and voltage-gated ion channels.
...
PMID:Modulation of serotonin-induced currents by metals in mouse neuroblastoma cells. 887 Sep 59
