Two muscarinic depolarizing mechanisms in mammalian sympathetic neurons

Hashiguchi, Takashi; Kobayashi, Haruo; Tosaka, Tsuneo; Libet, Benjamin

doi:10.1016/0006-8993(82)90329-8

Cited by 53 publications

(22 citation statements)

References 19 publications

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“…This was associated with an increased conductance, so that the current-voltage curves not only showed reduced outward rectification at depolarized potentials but then, after converging around -60 mV, began to diverge again at more negative potentials. An additional inward current of this type in response to muscarinic agonists, probably due to an increased cation conductance, has previously been reported in both frog (Adams et al 1982b;Jones, 1985) and rabbit (Hashiguchi, Kobayashi, Tosaka & Libet, 1982) sympathetic neurones, but has not previously been described in rat cells. Figure 3 shows responses to brief applications of muscarine to two cells in the same culture dish, in one of which 200 /tM-Gpp(NH)p was included in the patch-pipette solution.…”

Section: Resultsmentioning

confidence: 61%

On the transduction mechanism for muscarine‐induced inhibition of M‐current in cultured rat sympathetic neurones.

Brown

Marrion

Smart

1989

The Journal of Physiology

108

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SUMMARY1. Dissociated adult or fetal rat superior cervical ganglion cells were voltageclamped through a single patch pipette. The voltage-dependent K+ current, IM (Mcurrent), was maintained by including MgATP in the pipette solution and by buffering the solution pH to 6 7.2. Bath-applied muscarine (0 4 /IM) produced a reversible inhibition of IM.3. Addition of Gpp(NH)p (200 /tM) or GTP-y-S (500 /tM) to the pipette solution induced a slowly developing inhibition ofIM and prevented recovery from subsequent muscarine-induced inhibition.4. Addition of GDP-,/-S (500 uM) to the pipette solution reduced the amount of IM inhibition produced by 04 ,aM-muscarine by 42 % and reduced the associated inward shift of the holding current by 56 %.5. Cells responded normally to muscarine after pre-treatment for 4-27 h with 500 ng ml-1 pertussis toxin (PTx).6. IM was not diminished by extracellular addition of 1 mM-dibutyryl cyclic AMP, 8-bromo-cyclic AMP or dibutyryl cyclic GMP, or of 10 ,uM-forskolin.7. IM was not reduced by inclusion of Li' (2 mM) or inositol 1,4,5-trisphosphate (IP3, 100 /iM) in the patch pipette, nor by ionophoretic injection of 1P3 from an inserted micropipette.8. Addition of 4-,l-phorbol 12,13-dibutyrate (PDBu, 0 5-2 ,UM) to the extracellular medium partly inhibited IM and reduced an additional component of resting membrane current. This effect was not replicated by 4-a-phorbol 12,13-didecanoate. 9. It is concluded that the inhibition of IM by muscarine is mediated through activation of a PTx-insensitive GTP-binding protein. The effect of muscarine appears not to be mediated by cyclic nucleotides or 1P3 but may possibly involve the generation of diacylglycerols and activation of protein kinase C.

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Section: Resultsmentioning

confidence: 61%

On the transduction mechanism for muscarine‐induced inhibition of M‐current in cultured rat sympathetic neurones.

Brown

Marrion

Smart

1989

The Journal of Physiology

108

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“…The restriction of the M-current to just this one kind of smooth muscle would be somewhat surprising. In the larger context ofexcitable cells, IMdoes appear to be widespread, having first been identified in amphibian sympathetic neurones (Brown & Adams, 1980;Adams et al 1982 a, b) and subsequently observed in mammalian sympathetic neurones (Constanti & Brown, 1981;Hashiguchi, Kobayashi, Tosaka & Libet, 1982;Freschi, 1983), hippocampal, cortical and spinal neurones (Halliwell & Adams, 1982;Constanti & Galvan, 1983;Nowak & Macdonald, 1983). Moreover, suppression of a Ca2+-activated K+ current by muscarinic agonists has been documented in still other neurones (Morita et al 1982;North & Tokimasa, 1983;Cole & Nicoll, 1984;Pennefather et al 1985).…”

Section: Mechanisms Of Cholinergic Action In Smooth Musclementioning

confidence: 94%

Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.

Sims¹,

Singer²,

Walsh³

1985

The Journal of Physiology

100

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“…membrane hyperpolarization and diminished to negligible levels on depolarizing the cell to -30 mV or thereabouts, it might result from a mixed cation conductance or from a secondary increase in Cl-conductance; we have no firm information to indicate which of these possibilities is the more plausible. Hashiguchi et al (1982) have proposed two depolarizing components to the slow e.p.s.p. in rabbit ganglia, on the basis of current-voltage curves obtained in the presence and absence of exogenous muscarine: a voltage-dependent component at depolarized potentials, corresponding to the inhibition of IM, and a voltage-independent component at more hyperpolarized levels, in which current-voltage curves were displaced in a parallel manner (i.e.…”

Section: Outward Currentmentioning

confidence: 99%

“…IM is present in mammalian sympathetic neurones and (like that in frog neurones) is inhibited by exogenous muscarinic-receptor agonists Hashiguchi, Kobayashi, Tosaka & Libet, 1982;Freschi, 1983) (Kobayashi & Libet 1970; Ivanov & Skok, 1981), at variance with the 'M-current hypothesis', have been reported, which are reflected in the voltage dependence of the clamp currents produced by exogenous agonists (Brown & Selyanko, 1983, 1985.…”

Section: Introductionmentioning

confidence: 98%

Membrane currents underlying the cholinergic slow excitatory post‐synaptic potential in the rat sympathetic ganglion.

Brown¹,

Selyanko²

1985

The Journal of Physiology

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SUMMARY1. Non-nicotinic slow synaptic currents were recorded from voltage-clamped neurones in isolated rat superior cervical ganglia bathed in a solution containing d-tubocurarine and (usually) 1 /LM-neostigmine.2. Three components ofslow synaptic current could be detected following repetitive preganglionic stimulation: a net inward current resulting from inhibition of the voltage-dependent outward K+ current IM; a net outward current associated with a fall in membrane conductance when IM was deactivated by membrane hyperpolarization or inhibited with external Ba2+ or internal Cs+; and an occasional late inward current associated with an increased membrane conductance. As a result, synaptic current amplitudes showed complex changes with changes in membrane potential.3. Both the inward current associated with IM inhibition and the outward current were enhanced by neostigmine and blocked by atropine or pirenzepine, and therefore resulted from activation of muscarinic receptors.4. In unclamped neurones, equivalent stimulation produced a membrane depolarization and induced or facilitated repetitive spike discharges.5. It is concluded that the principal synaptic response to muscarinic receptor activation is IM inhibition, leading to a net inward current and increased excitability, but that this response may be modified under certain circumstances by other synaptic currents.

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Two muscarinic depolarizing mechanisms in mammalian sympathetic neurons

Cited by 53 publications

References 19 publications

On the transduction mechanism for muscarine‐induced inhibition of M‐current in cultured rat sympathetic neurones.

On the transduction mechanism for muscarine‐induced inhibition of M‐current in cultured rat sympathetic neurones.

Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.

Membrane currents underlying the cholinergic slow excitatory post‐synaptic potential in the rat sympathetic ganglion.

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