Enhancement of an L-type calcium current in AtT-20 cells; a novel effect of the m4 muscarinic receptor

Pemberton, Kyle; Jones, S. V. P.

doi:10.1007/bf00373991

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…Also depolarization of the membrane potential of RBL-2H3 cells endogenously expressing IRK1 has been demonstrated (Jones, 1997). Finally, activation of M1, M3 or M5 transfected into NIH 373 cells reduced the I Ca through G-protein activation of protein kinase C (PKC) (Pemberton and Jones, 1995; Pemberton and Jones, 1997). Pigeon and chicken vestibular type II hair cells demonstrate non-inactivating L-type Ca 2+ currents (Lang and Correia, 1989; Zampini et al, 2006; Masetto et al, 2005) as well as inwardly rectifying IRK1 (Kir2.1) currents (Masetto and Correia, 1997; Zampini et al, 2008; Correia et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Responses of pigeon vestibular hair cells to cholinergic agonists and antagonists

Correia

2011

Brain Research

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Acetylcholine (ACh) is the major neurotransmitter released from vestibular efferent terminals onto hair cells and afferents. Previous studies indicate that the two classes of acetylcholine receptors, nicotinic (nAChRs) and muscarinic receptors (mAChRs), are expressed by vestibular hair cells (VHCs). To identify if both classes of receptors are present in VHCs, whole cell, voltage-clampand current-clamp-patch recordings were performed on isolated pigeon vestibular type I and type II HCs during the application of the cholinergic agonists, acetylcholine and carbachol, and the cholinergic antagonists, d-tubocurarine and atropine. By applying in different combinations, these compounds were used to selectively activate either nAChRs or mAChRs. The effects of nAChR and mAChR activation on HC currents and zero electrode current potential (V z ) were monitored. It was found that presumed mAChR activation decreased both inward and outward currents in both type I and type II HCs, resulting in either a depolarization or hyperpolarization. Conversely, nAChR activation mainly increased both inward and outward currents in type II HCs, resulting in a hyperpolarization of their V z . nAChR activation also increased outward currents in type I HCs resulting in either a depolarization or hyperpolarization of their V z . The decrease of inward and outward currents and the depolarization of the V z in type I pigeon HCs by activation of mAChRs represents a new finding. Ion channel candidates in pigeon vestibular HCs that might underlie the modulation of the macroscopic ionic currents and V z by different AChR activation are discussed.

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Section: Discussionmentioning

confidence: 99%

Responses of pigeon vestibular hair cells to cholinergic agonists and antagonists

Correia

2011

Brain Research

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“…In most studies with L-type calcium channels of the C-class, increasing the concentration of cAMP results in an increase in calcium current amplitude. Increasing intracellular cAMP has been shown to reduce D-class L-type calcium channel activity [42]. It is possible that the C-class L-type calcium currents of the NIH 3T3 cell were already maximally stimulated under the recording conditions of the study.…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, in sympathetic neurons M1 and M4, as determined pharmacologically, have both been shown to inhibit L-type calcium channel activity although by different mechanisms [3,36]. Thirdly, the m4 muscarinic receptor endogenously expressed in AtT-20 cells induced a PTX-sensitive enhancement of L-type calcium current [42]. This appeared to be mediated by reductions in cAMP levels, but was opposite in effect to that observed to occur in heart.…”

Section: Introductionmentioning

confidence: 90%

“…Muscarinic receptors have been shown to modulate virtually all of the types of voltage-gated calcium channels identified to date (for review see [5,26,31]). The effects of muscarinic receptor stimulation include both inhibition and stimulation of the calcium channel activity, depending upon the type of channel under investigation [1,6,10,13,17,25,42,43,[51][52][53][54].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of the L-type calcium channel by the five muscarinic receptors (m1-m5) expressed in NIH 3T3 cells

Pemberton

Jones

1997

Pfl�gers Archiv European Journal of Physiology

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Modulation of L-type calcium channels by the five cloned muscarinic receptors was studied by expression of the receptors in NIH 3T3 cells. Application of acetylcholine (ACh) to cells transfected with m1-m5 resulted in a reduction in the L-type calcium current amplitude. Elevations in intracellular cAMP concentrations induced by 8-bromo-cAMP or forskolin resulted in no discernible change in the L-type calcium current. In addition, treatment with Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS), a protein kinase A (PKA) inhibitor, had no effect on the L-type currents. Conversely, application of phorbol dibutyrate, an activator of protein kinase C (PKC) or 8-bromo-cGMP, an activator of cGMP-dependent protein kinase (PKG), reduced the calcium currents. Incubation of the cells with KT5823, an inhibitor of PKG, resulted in a reduction of the response to 8-bromo-cGMP. The ACh-induced depression of L-type calcium current amplitude was sensitive to pertussis toxin (PTX) in cells transfected with the m2 or m4 receptor subtype. The m2-muscarinic-receptor-induced inhibition of the L-type calcium current was attenuated by preincubation of the cells with 8-bromo-cAMP and was unaffected by KT5823 or by calphostin C. The m1-muscarinic-receptor-induced inhibition of the L-type calcium conductance was insensitive to PTX treatment. However, the m1-induced response was blocked by preincubation of the cells with calphostin C. The present data indicate that the m2 (and possibly also the m4) muscarinic receptors inhibit the L-type calcium conductance by a reduction in cAMP concentration and that the m1 (and possibly also the m3 and m5) muscarinic receptors inhibit the L-type calcium channel via activation of PKC.

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“…activation of adenylate cyclase [7,8,13,18,25] or protein kinase C [20,26]. The Ca 2+ channel protein may be phosphorylated in these cases.…”

Section: Fig 6a Bmentioning

confidence: 98%

GABA B -mediated upregulation of the high-voltage-activated Ca 2+ channels in rat dorsal root ganglia

Fujikawa

Motomura

Ito

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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The mechanism underlying the enhancement of the high-voltage-activated (HVA) Ca2+ current (ICa) after application of baclofen, a GABAB agonist, in neurones of the rat dorsal root ganglia was studied by a combined use of the nystatin perforated patch clamp recording and our rapid superfusion system. Baclofen (50 microM) decreased the peak amplitude of HVA ICa and slowed the onset of the current, i.e. produced a typical G-protein-mediated inhibition of ICa. However, when baclofen was rapidly removed from the medium, the amplitude of the current was rather augmented, exceeding the control value obtained before application of the drug. This enhancement was not due to a shift of the voltage dependence of Ca2+ channel activation or a change in ionic permeability to other ions. The enhancement of HVA ICa by baclofen was sensitive to pertussis toxin treatment. The enhancement was evident during superfusion of baclofen. Since the inhibitory effect of baclofen on HVA ICa was not attenuated, even after a continuous application of baclofen for 10 min, the enhancement was not due to relief from tonic G-protein-mediated inhibition of the current or a desensitization of the GABAB receptor-effector system. An extremely prolonged time course of the enhancement of HVA ICa by baclofen strongly suggests an involvement of some intracellular signal transduction system.

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Enhancement of an L-type calcium current in AtT-20 cells; a novel effect of the m4 muscarinic receptor

Cited by 14 publications

References 37 publications

Responses of pigeon vestibular hair cells to cholinergic agonists and antagonists

Responses of pigeon vestibular hair cells to cholinergic agonists and antagonists

Inhibition of the L-type calcium channel by the five muscarinic receptors (m1-m5) expressed in NIH 3T3 cells

GABA B -mediated upregulation of the high-voltage-activated Ca 2+ channels in rat dorsal root ganglia

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