α1-Adrenoceptors in rat dorsal raphe neurons: Regulation of two potassium conductances

Z. Z. Pan, T. J. Grudt, John Williams

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

1. α1-Adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The α1-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101. 2. Under voltage clamp, α1-adrenoceptor agonists caused an inward current at -60 mV, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the α1-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of α1-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by α1-adrenoceptor agonists, whereas nifedipine and ω-conous toxin had no effect. In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA) did not inhibit the inward current. 3. The α1-induced depolarization was blocked (or occluded) by the inclusion of GTP-γ-S (100 μM) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late component of the after-hyperpolarization (late-AHP) that followed a single action potential. The α1-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization induced by α1-agonists was not changed; however, the late-AHP was reduced in duration and the α1-receptor-mediated augmentation of the late-AHP was decreased. 7. The results suggest that the depolarization of dorsal raphe neurons by α1-adrenoceptor activation is through a decrease in potassium conductance that is independent of the activation of the phospholipase C pathway. The augmentation of the late-AHP is mediated by release of calcium from intracellular stores and may serve to regulate activity during the depolarization induced by α1-adrenoceptor activation.

Original languageEnglish (US)
Pages (from-to)437-447
Number of pages11
JournalJournal of Physiology
Volume478
Issue number3
StatePublished - 1994

Fingerprint

Adrenergic Receptors
Phenylephrine
Potassium
Neurons
Caffeine
Calcium
Action Potentials
Ryanodine
Phorbol 12,13-Dibutyrate
Cadmium Chloride
Strontium
Magnesium Chloride
Ethane
Thapsigargin
Prazosin
Type C Phospholipases
Phorbol Esters
Patch-Clamp Techniques
Barium
Nifedipine

ASJC Scopus subject areas

  • Physiology

Cite this

α1-Adrenoceptors in rat dorsal raphe neurons : Regulation of two potassium conductances. / Pan, Z. Z.; Grudt, T. J.; Williams, John.

In: Journal of Physiology, Vol. 478, No. 3, 1994, p. 437-447.

Research output: Contribution to journalArticle

@article{34e29dde9c2b4f16be93c9b53b019fb5,
title = "α1-Adrenoceptors in rat dorsal raphe neurons: Regulation of two potassium conductances",
abstract = "1. α1-Adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The α1-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101. 2. Under voltage clamp, α1-adrenoceptor agonists caused an inward current at -60 mV, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the α1-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of α1-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by α1-adrenoceptor agonists, whereas nifedipine and ω-conous toxin had no effect. In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA) did not inhibit the inward current. 3. The α1-induced depolarization was blocked (or occluded) by the inclusion of GTP-γ-S (100 μM) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late component of the after-hyperpolarization (late-AHP) that followed a single action potential. The α1-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization induced by α1-agonists was not changed; however, the late-AHP was reduced in duration and the α1-receptor-mediated augmentation of the late-AHP was decreased. 7. The results suggest that the depolarization of dorsal raphe neurons by α1-adrenoceptor activation is through a decrease in potassium conductance that is independent of the activation of the phospholipase C pathway. The augmentation of the late-AHP is mediated by release of calcium from intracellular stores and may serve to regulate activity during the depolarization induced by α1-adrenoceptor activation.",
author = "Pan, {Z. Z.} and Grudt, {T. J.} and John Williams",
year = "1994",
language = "English (US)",
volume = "478",
pages = "437--447",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - α1-Adrenoceptors in rat dorsal raphe neurons

T2 - Regulation of two potassium conductances

AU - Pan, Z. Z.

AU - Grudt, T. J.

AU - Williams, John

PY - 1994

Y1 - 1994

N2 - 1. α1-Adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The α1-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101. 2. Under voltage clamp, α1-adrenoceptor agonists caused an inward current at -60 mV, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the α1-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of α1-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by α1-adrenoceptor agonists, whereas nifedipine and ω-conous toxin had no effect. In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA) did not inhibit the inward current. 3. The α1-induced depolarization was blocked (or occluded) by the inclusion of GTP-γ-S (100 μM) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late component of the after-hyperpolarization (late-AHP) that followed a single action potential. The α1-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization induced by α1-agonists was not changed; however, the late-AHP was reduced in duration and the α1-receptor-mediated augmentation of the late-AHP was decreased. 7. The results suggest that the depolarization of dorsal raphe neurons by α1-adrenoceptor activation is through a decrease in potassium conductance that is independent of the activation of the phospholipase C pathway. The augmentation of the late-AHP is mediated by release of calcium from intracellular stores and may serve to regulate activity during the depolarization induced by α1-adrenoceptor activation.

AB - 1. α1-Adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The α1-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101. 2. Under voltage clamp, α1-adrenoceptor agonists caused an inward current at -60 mV, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the α1-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of α1-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by α1-adrenoceptor agonists, whereas nifedipine and ω-conous toxin had no effect. In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA) did not inhibit the inward current. 3. The α1-induced depolarization was blocked (or occluded) by the inclusion of GTP-γ-S (100 μM) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late component of the after-hyperpolarization (late-AHP) that followed a single action potential. The α1-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization induced by α1-agonists was not changed; however, the late-AHP was reduced in duration and the α1-receptor-mediated augmentation of the late-AHP was decreased. 7. The results suggest that the depolarization of dorsal raphe neurons by α1-adrenoceptor activation is through a decrease in potassium conductance that is independent of the activation of the phospholipase C pathway. The augmentation of the late-AHP is mediated by release of calcium from intracellular stores and may serve to regulate activity during the depolarization induced by α1-adrenoceptor activation.

UR - http://www.scopus.com/inward/record.url?scp=0028168430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028168430&partnerID=8YFLogxK

M3 - Article

C2 - 7525947

AN - SCOPUS:0028168430

VL - 478

SP - 437

EP - 447

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 3

ER -