Biomedical subjects

C J Lingle

Publications and source records attributed to C J Lingle.

40 records · Page 3Linked to original sources

PubMed1986

Trapping of an open-channel blocker at the frog neuromuscular acetylcholine channel.

At the ganglionic nicotinic acetylcholine channel (Gurney, A. M., and H. P. Rang, 1984, Br. J. Pharmacol., 82:623-642) and on some cholinergic neuromuscular synapses of Crustacea (Lingle, C., 1983a, J. Physiol. (Lond.), 339:395-417; Lingle, C., 1983b, J. Physiol. (Lond.), 339:419-437), some agents that block cholinergic currents by an open-channel block mechanism appear to become trapped within the channel when it subsequently closes. It is unknown whether trapping of some open-channel blockers might also occur at the neuromuscular nicotinic acetylcholine channel. Here we show that the long-lived cholinergic blocking action of chlorisondamine, a ganglionic nicotinic blocker, can in part be most simply explained by an open-channel block mechanism followed by a subsequent trapping of the blocking molecule within the closed ion channel. Unique structural characteristics of the chlorisondamine molecule place several provocative constraints on the mechanism by which trapping may be occurring.

Animals↗

PubMed1986

A GABA-activated chloride-conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations.

Conductance increases to gamma-aminobutyric acid (GABA) were recorded in the gm6b and opener muscle of the spiny lobsters, Panulirus interruptus and P. argus. GABA-evoked responses were insensitive to picrotoxin at concentrations as high as 5 X 10(-5) M. Some blockade by picrotoxin was observed at higher concentrations. In normal physiological saline, the reversal potential of the Panulirus GABA-induced response was near the resting potential. The reversal potential was unaffected by reductions in sodium and calcium. Reduction of chloride by 50% resulted in a greater than 10 mV shift in the reversal potential of the GABA-induced response. Muscimol was able to mimic the action of GABA while baclofen was without effect. Bicuculline was a weak blocker. Avermectin B1a irreversibly increased the chloride permeability of the gm6b membrane. This conductance increase was blocked by picrotoxin over a range of concentrations similar to those required for blockade of the GABA-induced response. GABA-induced responses of the gm6b muscle of Homarus americanus were blocked almost completely by picrotoxin 10(-6) M. Sensitivity to picrotoxin is not invariably associated with GABA-activated chloride-mediated conductance increases. It is suggested that alteration in the binding-site for picrotoxin on the GABA-activated chloride-ion channel does not change other functional characteristics of the GABA-induced response.

Action Potentials↗

PubMed1986

Heterogeneous kinetic properties of acetylcholine receptor channels in Xenopus myocytes.

We have used the cell-attached patch-clamp technique to examine the kinetic and conductance properties of acetylcholine receptor channel currents in cultured Xenopus myocytes. At high agonist concentrations (5-100 microM) the currents occurred in bursts of openings. The probability that a channel existed in an ion-conducting conformation during a burst (Po) was adopted as an empirical measure of channel kinetic behaviour. All openings within a given burst were to the same mean current amplitude. However, different bursts could have openings with a mean conductance of either 46 pS (gamma 40) or 64 pS (gamma 60). For gamma 40 bursts there were three predominant populations which could be distinguished by their mean Po values (approximately 0.9, approximately 0.3, and less than 0.01 at 20 microM-acetylcholine). Po values increased as the acetylcholine concentration within the micropipette was increased. About 80% of bursts were from the highest Po population. gamma 60 bursts also occurred in three predominant modes. The highest Po population accounted for greater than 80% of all bursts and had a mean Po of approximately 0.6 at 20 microM-acetylcholine. For both gamma 40 and gamma 60 channels, bursts from the highest Po population had open-interval durations which were approximately 4 times longer than those from bursts from the medium Po population. Closed intervals from gamma 40, high Po bursts were approximately 4 times shorter than those from medium Po bursts. Occasional examples of switching between different kinetic modes were observed, suggesting that the Po populations may represent different activity patterns of a homogeneous channel population.

Acetylcholine↗

PubMed1986

Membrane currents in identified lactotrophs of rat anterior pituitary.

Qualitative features of the primary inward and outward current components of identified lactotrophs of the rat anterior pituitary were examined. Identification of lactotrophs in heterogeneous dissociated anterior pituitary cultures was accomplished by application of the reverse hemolytic plaque assay. Currents in lactotrophs were subsequently examined using whole-cell or patch recording techniques. Two components of inward calcium current were observed: a transient component and a sustained component. The transient component activated at voltages as negative as -50 mV and was the major contributor to total lactotroph calcium current. The sustained component activated at voltages above about -10 mV. The 2 currents could be qualitatively separated by differences in inactivation properties and in sensitivity to cadmium. At least 3 components of outward current were distinguished. Either 30 mM TEA or 0 calcium eliminated a major portion of sustained outward current. This is likely to represent primarily calcium- and voltage-activated potassium current. The remaining current could be further differentiated into a transient current component that could be inactivated with conditioning potentials above -60 mV. A slowly activating and deactivating potassium current remained following inactivation of the transient current. Although the time course of the transient current is reminiscent of "A" current, activation of this current required potentials above -30 mV. Candidates for the single-channel currents that underlie the whole-cell outward currents were observed in cell-attached recordings. When combined with patch-clamp electrophysiological methods, the reverse hemolytic plaque assay promises to be a powerful technique for the electrophysiological characterization of specific cell subtypes in heterogeneous dissociated cell populations.

Animals↗