Lonnie P Wollmuth

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The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast(More)
The structure of the NMDA receptor channel M2 segment was investigated by probing the extracellular and cytoplasmic faces of cysteine-substituted NR1-NR2C channels with charged sulfhydryl-specific reagents. The pattern of accessible positions suggests that the M2 segment forms a channel-lining loop originating and ending on the cytoplasmic side of the(More)
In NMDA receptor channels, the M2 loop forms the narrow constriction and the cytoplasmic vestibule. The identity of an extracellular vestibule leading toward the constriction remained unresolved. Using the substituted cysteine accessibility method (SCAM), we identified channel-lining residues of the NR1 subunit in the region preceding M1 (preM1), the(More)
1. In outside-out patches excised from human embryonic kidney (HEK) 293 cells expressing Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR) channels, currents activated by 1 ms glutamate pulses at negative membrane potentials facilitated during and following a repetitive (2 to 100 Hz) agonist application. The degree of(More)
1. The voltage-dependent block of N-methyl-D-aspartate (NMDA) receptor channels by extracellular Mg2+ is a critical determinant of its contribution to CNS synaptic physiology. The function of the narrow constriction of the channel in determining the block was investigated by analysing the effects of a set different amino acid substitutions at exposed(More)
The actions of N-ethylmaleimide (NEM), a sulfhydryl alkylating agent, on G-protein-mediated inhibition of N-type Ca2+ channels in adult rat superior cervical ganglion (SCG) neurons were studied using whole-cell voltage clamp. In SCG neurons, inhibition of ICa occurs by at least three separable pathways: one pertussis toxin (PTX) sensitive and voltage(More)
1. The molecular determinants for the narrow constriction of recombinant N-methyl-D-aspartate (NMDA) receptor channels composed of wild-type and mutant NR1- and NR2A-subunits were studied in Xenopus oocytes. 2. The relative permeability of differently sized organic cations was used as an indicator of the size of the narrow constriction. From measured(More)
Many N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. The M3(More)
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that contribute to fundamental physiological processes such as learning and memory and, when dysfunctional, to pathophysiological conditions such as neurodegenerative diseases, stroke, and mental illness. NMDARs are obligate heteromultimers typically composed of NR1 and NR2 subunits with(More)
Ionic selectivity of Ih channels of tiger salamander rod photoreceptors was investigated using whole-cell voltage clamp. Measured reversal potentials and the Goldman-Hodgkin-Katz voltage equation were used to calculate permeability ratios with 20 mM K+ as a reference. In the absence of external K+, Ih is small and hard to discern. Hence, we defined Ih as(More)