Steady-state characteristics of the proton receptor in the somatic membrane of rat sensory neurons

Korkushko, A. O.; Kryshtal, O. A.; Chernevskaya, N. I.

doi:10.1007/bf01066123

Cited by 6 publications

(8 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The kinetics of desensitization demonstrated by ASICs expressed in DRG neurons has very weak dependence on the acting pH (Korkushko et al 1983). Figure 1(a) demonstrates this with the example of a 'fast' response in the range of activating pH levels from 6.6 to 5.2.…”

Section: Resultsmentioning

confidence: 84%

“…The kinetics of desensitization demonstrated by ASICs expressed in DRG neurons has very weak dependence on the acting pH (Korkushko et al . 1983).…”

Section: Resultsmentioning

confidence: 99%

“…Figure 1(a) demonstrates this with the example of a 'fast' response in the range of activating pH levels from 6.6 to 5.2. This is not surprising because the steady-state desensitization dependence is titrated by protons at the pH levels that are higher than the activation 'threshold', which is around neutral pH at normal concentrations of external divalents (Korkushko et al 1983). It should be noted that various individual subunits and their combinations may have such dependence on the acting pH (Zhang and Canessa 2002;Hesselager et al 2003).…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Modulatory action of RFamide‐related peptides on acid‐sensing ionic channels is pH dependent: the role of arginine

Ostrovskaya¹,

Moroz²,

Krishtal³

2004

Journal of Neurochemistry

View full text Add to dashboard Cite

Acid-sensing ionic channels (ASICs) are involved in such functions of the sensory nervous system as mechanoreception, nociception and perception of acid taste. Phe-Met-Arg-Phe amiderelated (FMRFa-related) peptides in lM concentrations slow down the rate of ASICs desensitization. Here we report that this effect is strongly pH dependent: the lower the pH used to activate ASICs, the larger is the modulatory effect of Arg-Phe amide-related (RFarelated) peptides. Pre-application of the peptides results in a change to the desensitization kinetics of the ASICs-operated current from monoexponential to biexponential: the fast component retains the control kinetics, whereas the slow one is induced by the peptide. The lower the pH, the larger is the slow component, whereas there is practically no modulation at pH 6.6. PheMet-Val-Phe amide (FMVFa), which has neutral valine instead of arginine, similarly modulates the kinetics of ASICs, but does not reveal pH dependence of this action. Thus, positively charged arginine regulates the access of the RFa-related peptides to the modulatory site. We suggest that the pH dependence of the modulatory action of RFa-related peptides can be associated with the interaction of a positively charged arginine with histidine residues in the molecule of ASIC. Keywords: acid-sensing ionic channels, pH dependence, protonactivated current, Arg-Phe amide-peptides, sensory neurons. The acid-sensing ionic channels, ASICs, belonging to the epithelial sodium channel (ENaC)/degenerin family (Waldmann and Lazdunski 1998) are proven to be functionally important both in the CNS and at the periphery. The time course of the ASICs desensitization in native sensory neurons is variable (Krishtal and Pidoplichko 1981) and depends on the subtypes of ASICs expressed (Waldmann and Lazdunski 1998). Selective elimination of various subtypes of ASICs affects a variety of sensory functions such as mechanoreception, pain sensitivity and perception of acid taste (Price et al. 2000(Price et al. , 2001Wemmie et al. 2002). Except for protons, the endogenous ligands of ASICs remain unknown and it is unclear how these channels contribute to sensory processing within the physiological range of pH. The findings of different authors indicate that mollusc-derived peptide, FMRFamide (FMRFa) and its analogs efficiently slow down the rate of desensitization of ASICs in dorsal root ganglion (DRG) neurons (Askwith et al. 2000;Xie et al. 2002Xie et al. , 2003 and in hippocampal neurons (Askwith et al. 2004). FMRFa increases both peak value and late component of the response to acids in Purkinje neurons (Allen and Attwell 2002). These observations are confirmed for some of the mammalian endogenous RFa related peptides (Catarsi et al. 2001;Deval et al. 2003;Xie et al. 2003). To access the structure-activity relationship in this ligand group, we tested the action of several RFa-related peptides on the kinetic parameters of ASICs in the sensory neurons from dorsal root ganglia (DRG) and trigeminal ganglia. Here we report that the ...

show abstract

Section: Resultsmentioning

confidence: 84%

“…The kinetics of desensitization demonstrated by ASICs expressed in DRG neurons has very weak dependence on the acting pH (Korkushko et al . 1983).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Modulatory action of RFamide‐related peptides on acid‐sensing ionic channels is pH dependent: the role of arginine

Ostrovskaya¹,

Moroz²,

Krishtal³

2004

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…On the basis of their observations of ASIC3, ASIC1a, and native neuronal acid-evoked currents, Immke and McCleskey (2003) recently proposed that rather than directly activating the current, protons open ASIC channels by catalyzing the relief of channel block by calcium. The observation that a reduction in extracellular calcium enables ASICs to activate at less acidic pH levels suggests that local calcium homeostasis may play a significant role in the control of these channels (Korkushco et al, 1983;Babini et al, 2002).…”

Section: Physiological Rolementioning

confidence: 99%

The Discovery and Characterization of a Proton-Gated Sodium Current in Rat Retinal Ganglion Cells

Lilley¹,

Tissier²,

Robbins³

2004

J. Neurosci.

View full text Add to dashboard Cite

The conduction of acid-evoked currents in central and sensory neurons is now primarily attributed to a family of proteins called acid-sensing ion channels (ASICs). In peripheral neurons, their physiological function has been linked to nociception, mechanoreception, and taste transduction; however, their role in the CNS remains unclear. This study describes the discovery of a proton-gated current in rat retinal ganglion cells termed I Na(Hϩ) , which also appears to be mediated by ASICs. RT-PCR confirmed the presence of ASIC mRNA (subunits la, 2a, 2b, 3, and 4) in the rat retina. Electrophysiological investigation showed that all retinal ganglion cells respond to rapid extracellular acidification with the activation of a transient Na ϩ current, the size of which increases with increasing acidification between pH 6.5 and pH 3.0. I Na(Hϩ) desensitizes completely in the continued presence of acid, its current-voltage relationship is linear and its reversal potential shifts with E Na . I Na(Hϩ) is reversibly inhibited by amiloride (IC 50 , 188 M) but is resistant to block by TTX (0.5 M), Cd 2ϩ (100 M), procaine (10 mM), and is not activated by capsaicin (0.5 M). I Na(Hϩ) is not potentiated by Zn 2ϩ (300 M) or Phe-MetArg-Phe-amide (50 M) but is inhibited by neuropeptide-FF (50 M). Acute application of pH 6.5 to retinal ganglion cells causes sustained depolarization and repetitive firing similar to the trains of action potentials normally associated with current injection into these cells. The presence of a proton-gated current in the neural retina suggests that ASICs may have a more diverse role in the CNS.

show abstract

“…A decrease in pH of the extracellular milieu is known to activate proton-sensitive ion channels (ASICs) present in the membranes of peripheral sensory neurons [1][2][3] and also of some types of central neurons [4][5][6]. There are several types of ASICs; all these channels are selectively permeable for Na 2+ [7][8][9], while some of them are also permeable for Ca 2+ [10].…”

Section: Introductionmentioning

confidence: 98%

Dynamics of desensitization and recovery of proton-activated ion channels in pheochromocytoma cells

2007

View full text Add to dashboard Cite

Proton-activated ion channels of the ASIC 1a subtype in pheochromocytoma PC12 cells were inactivated under the long-lasting influence of an acidic milieu (pH 6.0) because of desensitization developing in a monoexponential mode with τ = 1.7 ± 0.3 sec. The recovery of currents after desensitization was also monoexponential, with τ = 4.9 ± 0.8 sec. Approximation of the dose−effect curve by the Hill equation showed that activation of a channel of this type needs, most probably, binding of three hydrogen ions.

show abstract

Steady-state characteristics of the proton receptor in the somatic membrane of rat sensory neurons

Cited by 6 publications

References 5 publications

Modulatory action of RFamide‐related peptides on acid‐sensing ionic channels is pH dependent: the role of arginine

Modulatory action of RFamide‐related peptides on acid‐sensing ionic channels is pH dependent: the role of arginine

The Discovery and Characterization of a Proton-Gated Sodium Current in Rat Retinal Ganglion Cells

Dynamics of desensitization and recovery of proton-activated ion channels in pheochromocytoma cells

Contact Info

Product

Resources

About