To Tetraethylammonium Research Articles

Spontaneous miniature outward currents in cultured bullfrog neurons

Spontaneous miniature hyperpolarizations were observed in cultured bullfrog neurons. Depolarization increased the frequency and amplitude of the events. Under voltage-clamp, these events were manifested as spontaneous miniature outward currents or SMOCs which were usually <2nA, had a rapid rising phase and a slower voltage-dependent exponential decay. Analysis of inter-event interval suggested that SMOCs occured randomly, while analysis of their amlitudes yielded exponential amplitude distributions. Mean SMOC amplitudes and SMOC frequency increased with depolarization, even with 100 μM CdCl 2 present. Time constants of SMOC decay resembled time constants obtained from voltage-jump experiments on Ca 2+-loaded cells, and together with the sensitivity of SMOCs to tetraethyl ammonium (TEA), suggested that SMOCs are due to activation of fast Ca 2+-gated potassium channels. We propose that a SMOC occurs when 10–5000 of these channels are activated by punctate intracellular Ca 2+ release.

Mammalian optic nerve fibers display two pharmacologically distinct potassium channels

A suction electrode recording technique was used to study action potential characteristics of rat optic nerve fibers. Two pharmacologically distinct potassium channels are described. One is sensitive to 4-aminopyridine (4-AP) and the other to tetraethylammonium (TEA). 4-AP application leads to a substantial broadening of the optic nerve action potential, but TEA does not. 4-AP application also elicits a TEA-sensitive post-spike positivity, i.e. an intracellular hyperpolarization. From these results we suggest that the 4-AP-sensitive channel, not the TEA-sensitive channel, is primarily responsible for action potential repolarization of mammalian optic nerve fibers.

N1-methylnicotinamide transport by isolated perfused snake proximal renal tubules.

N1-methylnicotinamide (NMN) transport was studied in isolated perfused snake (Thamnophis spp.) proximal renal tubules. Unidirectional lumen-to-bath (Jl----bNMN) and bath-to-lumen (Jb----lNMN) fluxes saturated. Although Jl----bNMN and Jb----lNMN were similar, mean Jl----bNMN tended to exceed mean Jb----lNMN at all concentrations studied. Direct measurements confirmed a net reabsorptive flux equal to the difference between the unidirectional fluxes. This transport, opposite in direction to tetraethylammonium (TEA) transport, was not inhibited by TEA. Transport into the cells across both the luminal and peritubular membranes during flux measurements was apparently down an electrochemical gradient by a mediated process that was sodium dependent. Inhibition with NMN analogues suggested that transport into the cells across the luminal membrane during Jl----bNMN was more specific than transport into the cells across the peritubular membrane during Jb----lNMN. Transport out of the cells across both the luminal and peritubular membranes during flux measurements was apparently against an electrochemical gradient.

A potent transient outward current regulates excitability of dorsal raphe neurons

Activity of neurons in the dorsal raphe nucleus of the rat was recorded intracellularly in a brainstem slice. The neurons had a high input resistance, a linear I-V curve in the hyperpolarizing direction and a long membrane time constant. Broad action potentials were followed by a large afterhyperpolarization (AHP). This AHP removes partial inactivation of a potent transient outward rectifier that is activated by a subsequent depolarization of the neuron; it clamps the cell membrane at a potential slightly below firing level and blocks generation of action potentials for up to 100 ms. The transient rectification was sensitive to 4-aminopyridine (4-AP) but not to tetraethylammonium (TEA). It appears to share similar properties with those of IA seen elsewhere and to function in the regulation of interspike intervals of dorsal raphe (DR) neurons in vitro.

Malignant mesothelioma and gas-mask assemblers.

We have examined gating and pharmacological characteristics of somatic K⁺ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K⁺ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (half-maximal inhibitory concentrations &lt;0.1 mm) predominated, contributing an average of 58% to the total K⁺ current in these cells. By contrast, in pyramidal neurons of the CA1 region a rapidly inactivating A-type K⁺ current component that was TEA-resistant prevailed, contributing 61% to the total K⁺current. Both types of neurons also showed small amounts of the K⁺ current component mainly found in the other type of neuron and, in addition, a slow delayed rectifier K⁺ current component with intermediate properties (slow inactivation, intermediate sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K⁺ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.