Phorbol ester‐induced M‐current suppression in bull‐frog sympathetic ganglion cells: insensitivity to kinase inhibitors

Chen, Hsinyo; Jassar, Balvinder S.; Kurenny, Dmitry E.; Smith, Peter A.

doi:10.1111/j.1476-5381.1994.tb16173.x

Cited by 14 publications

(7 citation statements)

References 29 publications

(73 reference statements)

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“…PMA also depolarized the cells like Ang II. A similar depolarization by PMA was reported in bull‐frog sympathetic neurones and was determined to be independent of PKC (Chen et al 1994) just as the Ang II‐induced depolarization we report here is PKC independent. As described above, the PKC inhibitor H7 blocked Ang II‐induced inhibition of IA and prevented Ang II‐induced AP discharge but did not prevent the depolarization.…”

Section: Discussionsupporting

confidence: 89%

Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Ma¹,

Bielefeldt

Tan³

et al. 2006

The Journal of Physiology

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Ang II directly activates neurones in sympathetic ganglia. Our goal was to define the electrophysiological basis of this activation. Neurones from mouse aortic-renal and coeliac ganglia were identified as either 'tonic' or 'phasic'. With injections of depolarizing currents, action potentials (APs) were abundant and sustained in tonic neurones (TNs) and scarce or absent in phasic neurones (PNs). Resting membrane potentials were equivalent in TNs (−48 ± 2 mV, n = 18) and PNs (−48 ± 1 mV, n = 23) while membrane resistance was significantly higher in TNs. Ang II depolarized and increased membrane resistance equally in both TNs (n = 8) and PNs (n = 8) but it induced APs only in TNs, and enhanced current-evoked APs much more markedly in TNs (P < 0.05). The AT 1 receptor antagonist losartan (2 μM, n = 6) abolished all responses to Ang II, whereas the AT 2 receptor blocker PD123,319 had no effect. The transient K + current (IA), which was more than twice as large in TNs as in PNs, was significantly inhibited by Ang II in TNs only whereas the delayed sustained K + current (IK), which was comparable in both TNs and PNs, was not inhibited. M currents were more prominent in

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Section: Discussionsupporting

confidence: 89%

Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Ma¹,

Bielefeldt

Tan³

et al. 2006

The Journal of Physiology

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“…It may therefore directly transduce the effects of agonists such as ATP. Although we have found that DAG-induced g M suppression is insensitive to the PKC inhibitors, H-7 and staurosporin (Chen et al 1994;Selyanko et al 1990), different results have been reported by other laboratories (Bosma and Hille 1989). We therefore examined the effects of chelerythrine on 1,2-diocta-nyl-sn-glycerol (DOG)-induced g M suppression using the same treatment protocol as was for established PKC inhibition in the present study (Fig.…”

Section: Is Dag Involved In Atp-induced G M Suppression?contrasting

confidence: 73%

“…It has been suggested that DAG can interact directly with M channels (Chen et al 1994;Clapp et al 1992). It may therefore directly transduce the effects of agonists such as ATP.…”

Section: Is Dag Involved In Atp-induced G M Suppression?mentioning

confidence: 99%

ATP-Inhibition of M Current in Frog Sympathetic Neurons Involves Phospholipase C But Not Ins P₃, Ca²⁺, PKC, orRas

Stemkowski

Tse

Peuckmann

et al. 2002

Journal of Neurophysiology

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Suppression of the voltage-activated, noninactivating K(+) conductance (M conductance; g(M)) by muscarinic agonists, P(2Y) agonists or bradykinin increases neuronal excitability. All agonist effects are mediated, at least in part, via the Gq/(11) class of G protein. We found, using whole cell or perforated patch recording from bullfrog sympathetic B neurons that ATP-induced suppression of g(M) was attenuated by the phospholipase C (PLC) inhibitor, U73122 (IC(50) approximately 0.14 microM) but not by the inactive isomer, U73343. The ability of extracellularly applied U73122 to inhibit PLC was confirmed by its antagonism of ATP-induced elevation of intracellular Ca(2+) as measured by fura-2 photometry. ATP-induced g(M) suppression was not antagonized by the protein kinase C (PKC) inhibitor, chelerythrine (5 microM extracellular +10 microM intracellular), by the Ca(2+)-ATPase inhibitor, thapsigargin (5 microM), or by inositol trisphosphate (InsP(3)) receptor antagonists, heparin (approximaterly 300 microM) or xestospongin C (1.8 microM). The effect of ATP on g(M) was thus dependent on PLC yet independent of PKC and of InsP(3)-induced release of intracellular Ca(2+). We therefore tested the involvement of a PKC-independent action of diacylglycerol (DAG) that could occur via activation of Ras. This low-molecular-weight G protein is activated following DAG binding to Ras-GRP, a neuronal Ras-GTP exchange factor. However, impairment of Ras function by culturing neurons with isoprenylation inhibitors (perillic acid, 0.1 mM, or alpha-hydroxyfarnesyl-phosphonic acid, 10 microM) failed to affect ATP-induced g(M) suppression. Inhibition of MEK (mitogen-activated protein kinase), a downstream target of Ras, by using PD 98059 (10 microM) was also ineffective. The transduction mechanism used by ATP to suppress g(M) in frog sympathetic neurons therefore differs from the PLC-independent mechanism used by muscarine and from the PLC and Ca(2+)-dependent mechanism used by bradykinin and UTP in mammalian ganglia. The possibility remains that "lipid-signaling" mechanisms, perhaps involving PLC-induced depletion of phosphatidylinositol bisphosphate, are involved in PLC-mediated inhibition of g(M) by ATP in amphibian sympathetic neurons.

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“…In NG108‐15 cells, moreover, PKC 19–31 peptide, an effective inhibitor of PKC, elicits a shift in the voltage dependence of the M‐current such that the V ½ goes from −34 mV to −44 mV (Schmitt & Meves, 1993). However, because the inhibition induced by phorbol esters or diacylglycerols is partial at most, and because PKC inhibitors fail to prevent receptor‐mediated M‐current inhibition, PKC has not been considered necessary for muscarinic inhibition (Bosma & Hille, 1989; Chen et al 1994). In the present study, we found that PKC positively shifts the G – V relationship of KCNQ channels; in other words, PKC made KCNQ channels reluctant to open.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

Nakajo

Kubo

2005

The Journal of Physiology

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It is well established that stimulation of G q -coupled receptors such as the M1 muscarinic acetylcholine receptor inhibits KCNQ/M currents. While it is generally accepted that this muscarinic inhibition is mainly caused by the breakdown of PIP 2 , the role of the subsequent activation of protein kinase C (PKC) is not well understood. By reconstituting M currents in Xenopus oocytes, we observed that stimulation of coexpressed M1 receptors with 10 µM oxotremorine M (oxo-M) induces a positive shift (4-30 mV, depending on which KCNQ channels are expressed) in the conductance-voltage relationship (G-V ) of KCNQ channels. When we applied phorbol 12-myristate 13-acetate (PMA), a potent PKC activator, we observed a large positive shift (17.8 ± 1.6 mV) in the G-V curve for KCNQ2, while chelerythrine, a PKC inhibitor, attenuated the shift caused by the stimulation of M1 receptors. By contrast, reducing PIP 2 had little effect on the G-V curve for KCNQ2 channels; although pretreating cells with 10 µM wortmannin for 30 min reduced KCNQ2 current amplitude by 80%, the G-V curve was shifted only slightly (5 mV). Apparently, the shift induced by muscarinic stimulation in Xenopus oocytes was mainly caused by PKC activation. When KCNQ2/3 channels were expressed in HEK 293T cells, the G-V curve seemed already to be shifted in a positive direction, even before activation of PKC, and PMA failed to shift the curve any further. That alkaline phosphatase in the patch pipette shifted the G-V curve in a negative direction suggests KCNQ2/3 channels are constitutively phosphorylated in HEK 293T cells.

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Phorbol ester‐induced M‐current suppression in bull‐frog sympathetic ganglion cells: insensitivity to kinase inhibitors

Cited by 14 publications

References 29 publications

Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

ATP-Inhibition of M Current in Frog Sympathetic Neurons Involves Phospholipase C But Not Ins P₃, Ca²⁺, PKC, orRas

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

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Phorbol ester‐induced M‐current suppression in bull‐frog sympathetic ganglion cells: insensitivity to kinase inhibitors

Cited by 14 publications

References 29 publications

Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

ATP-Inhibition of M Current in Frog Sympathetic Neurons Involves Phospholipase C But Not Ins P3, Ca2+, PKC, orRas

Protein kinase C shifts the voltage dependence of KCNQ/M channels expressed in Xenopus oocytes

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ATP-Inhibition of M Current in Frog Sympathetic Neurons Involves Phospholipase C But Not Ins P₃, Ca²⁺, PKC, orRas