Dihydropyridine‐sensitive low‐threshold calcium channels in isolated rat hypothalamic neurones.

Akaike, Norio; Kostyuk, P. G.; Osipchuk, Y V

doi:10.1113/jphysiol.1989.sp017610

Cited by 339 publications

(164 citation statements)

References 28 publications

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“…These studies have allowed estimates of the affinity of the open channel for Ca 2ϩ . The average K D value from seven studies is 4.9 mM, with considerable variability (range 0.3Ϫ10 mM) (4,22,54,152,160,389,429).…”

Section: J Single-channel Recordingsmentioning

confidence: 97%

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Perez‐Reyes

2003

Physiological Reviews

1,501

1,446

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T-type Ca2+ channels were originally called low-voltage-activated (LVA) channels because they can be activated by small depolarizations of the plasma membrane. In many neurons Ca2+ influx through LVA channels triggers low-threshold spikes, which in turn triggers a burst of action potentials mediated by Na+ channels. Burst firing is thought to play an important role in the synchronized activity of the thalamus observed in absence epilepsy, but may also underlie a wider range of thalamocortical dysrhythmias. In addition to a pacemaker role, Ca2+ entry via T-type channels can directly regulate intracellular Ca2+ concentrations, which is an important second messenger for a variety of cellular processes. Molecular cloning revealed the existence of three T-type channel genes. The deduced amino acid sequence shows a similar four-repeat structure to that found in high-voltage-activated (HVA) Ca2+ channels, and Na+ channels, indicating that they are evolutionarily related. Hence, the α1-subunits of T-type channels are now designated Cav3. Although mRNAs for all three Cav3 subtypes are expressed in brain, they vary in terms of their peripheral expression, with Cav3.2 showing the widest expression. The electrophysiological activities of recombinant Cav3 channels are very similar to native T-type currents and can be differentiated from HVA channels by their activation at lower voltages, faster inactivation, slower deactivation, and smaller conductance of Ba2+. The Cav3 subtypes can be differentiated by their kinetics and sensitivity to block by Ni2+. The goal of this review is to provide a comprehensive description of T-type currents, their distribution, regulation, pharmacology, and cloning.

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Section: J Single-channel Recordingsmentioning

confidence: 97%

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Perez‐Reyes

2003

Physiological Reviews

1,501

1,446

View full text Add to dashboard Cite

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“…This difference may be due to neutralization of surface charges by the high Ba or Ca concentration needed to reveal the currents (Hale, 1984;McDonald et al, 1986;Akaike et al, 1989). When the external Ca was reduced, a lowering of the threshold, concomitant with a decrease of the current amplitude, was observed (Fig.…”

Section: Influence Of the External Divalent Cation Concentrationmentioning

confidence: 99%

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Béhé

DeSimone

Avenet

et al. 1990

The Journal of General Physiology

171

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Taste buds were isolated from the fungiform papilla of the rat tongue and the receptor cells (TRCs) were patch clamped. Seals were obtained on the basolateral membrane of 281 TRCs, protruding from the intact taste buds or isolated by micro-dissection. In whole-cell configuration 72% of the cells had a TTX blockable transient Na inward current (mean peak amplitude 0.74 hA). All cells had outward K currents. Their activation was slower than for the Na current and a slow inactivation was also noticeable. The K currents were blocked by tetraethylammonium, Ba, and 4-aminopyridine, and were absent when the pipette contained Cs instead of K. With 100 mM Ba or 100 mM Ca in the bath, two types of inward current were observed. An L-type Ca current (ICaL) activated at -20 mV had a mean peak amplitude of 440 pA and inactivated very slowly. At 3 mM Ca the activation threshold of ICa L was near -40 mV. A transient T-type current (/CAT) activated at -50 mV had an average peak amplitude of 53 pA and inactivated with a time constant of 36 ms at -30 inV. ICR L was blocked more efficiently by Cd and D600 than/Ca T. ICa T was blocked by 0.2 mM Ni and half blocked by 200 #M amiloride. In whole-cell voltage clamp, Na-saccharin caused (in 34% of 55 cells tested) a decrease in outward K currents by 21%, which may be expected to depolarize the TRCs. Also, Na-saccharin caused some taste cells to fire action potentials (on-ceLl, 7 out of 24 cells; whole-ceLl, 2 out of 38 cells responding to saccharin) of amplitudes sufficient to activate/CAL. ThUS the action potentials will cause Ca inflow, which may trigger release of transmitter.

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“…In contrast to the better studied high voltageactivated (HVA) 1 Ca 2ϩ channels (L-, N-, P/Q-, and R-type), T-type channels activate at relatively negative membrane potentials and are often referred to as "low voltage-activated" (LVA). The distinctive permeation properties of T-type Ca 2ϩ channels were critical for their original identification as distinct entities (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In native preparations, T-type channels are equally permeable to Ca 2ϩ and Ba 2ϩ ions, unlike all known HVA channels, for which unitary Ba 2ϩ fluxes are larger than those supported by Ca 2ϩ (17).…”

mentioning

confidence: 99%

Differences in Apparent Pore Sizes of Low and High Voltage-activated Ca2+ Channels

Cataldi

Perez‐Reyes

Tsien

2002

Journal of Biological Chemistry

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Pore size is of considerable interest in voltage-gated Ca 2؉ channels because they exemplify a fundamental ability of certain ion channels: to display large pore diameter, but also great selectivity for their ion of choice. We determined the pore size of several voltagedependent Ca 2؉ channels of known molecular composition with large organic cations as probes. T-type channels supported by the Ca V 3.1, Ca V 3.2, and Ca V 3.3 subunits; L-type channels encoded by the Ca V 1.2, ␤ 1 , and ␣ 2 ␦ 1 subunits; and R-type channels encoded by the Ca V 2.3 and ␤ 3 subunits were each studied using a Xenopus oocyte expression system. The weak permeabilities to organic cations were resolved by looking at inward tails generated upon repolarization after a large depolarizing pulse. Large inward NH 4 ؉ currents and sizable methylammonium and dimethylammonium currents were observed in all of the channels tested, whereas trimethylammonium permeated only through L-and Rtype channels, and tetramethylammonium currents were observed only in L-type channels. Thus, our experiments revealed an unexpected heterogeneity in pore size among different Ca 2؉ channels, with L-type channels having the largest pore (effective diameter ‫؍‬ 6.2 Å), T-type channels having the tiniest pore (effective diameter ‫؍‬ 5.1 Å), and R-type channels having a pore size intermediate between these extremes. These findings ran counter to first-order expectations for these channels based simply on their degree of selectivity among inorganic cations or on the bulkiness of their acidic side chains at the locus of selectivity. T-type Ca2ϩ channels are found in many cell types and are important for cellular functions as diverse as cell proliferation, cardiac pacemaker activity, and rhythmic firing of neural networks (1, 2). In contrast to the better studied high voltageactivated (HVA) 1 Ca 2ϩ channels (L-, N-, P/Q-, and R-type), T-type channels activate at relatively negative membrane potentials and are often referred to as "low voltage-activated" (LVA). The distinctive permeation properties of T-type Ca 2ϩ channels were critical for their original identification as distinct entities (3-16). In native preparations, T-type channels are equally permeable to Ca 2ϩ and Ba 2ϩ ions, unlike all known HVA channels, for which unitary Ba 2ϩ fluxes are larger than those supported by Ca 2ϩ (17). Despite general agreement about these differences (1), relatively little is known about the underlying basis of ion selectivity and permeation in T-type channels. New impetus for approaching such questions is provided by the molecular cloning of three different pore-forming Ca V subunits with biophysical properties that clearly identify them as T-type channels (18 -20), Ca V 3.1, Ca V 3.2, and Ca V 3.3 (␣ 1G , ␣ 1H , and ␣ 1I , respectively, in the former voltage-dependent calcium channel nomenclature). These subunits form a closely related family with only limited sequence homology to the subfamilies of HVA channels (ϳ28%). In the regions thought to be important for permeation, the Ca V...

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Dihydropyridine‐sensitive low‐threshold calcium channels in isolated rat hypothalamic neurones.

Cited by 339 publications

References 28 publications

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Differences in Apparent Pore Sizes of Low and High Voltage-activated Ca2+ Channels

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