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Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents.

Qiao GF, Li BY, Zhou YH, Lu YJ, Schild JH - Int. J. Biol. Sci. (2009)

Bottom Line: The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9.Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV).These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.

ABSTRACT
Persistent tetrodotoxin-resistant (TTX-R) Na(+) (Na(v)1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na(+) although the functional expression of this current was observed in the presence of PGE(2) or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na(+)). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na(+) currents were expressed in 9 out of 38 VANs bathed in 150 mM Na(+). The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV). This indicates that persistent TTX-R Na(+) channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

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The current density of TTX-S and TTX-R Na+ channels functionally expressed in low extracellular Na+ (50 mM Na+) and physiological extracellular Na+ environment. TTX-S Na+ currents (n = 7 for 50 mM Na+ and n = 8 for 150 mM Na+) were recorded from the VAN expressed TTX-S Na+ channel only; TTX-R Na+ currents (n = 34 for 50 mM Na+ and n = 21 for 150 mM Na+) were recorded from the VAN co-expressed TTX-S and TTX-R Na+ channel; and persistent TTX-R Na+ currents (n = 9) were recorded from the VAN co-expressed TTX-S, TTX-R, and persistent TTX-R Na+. TTX-R Na+ currents were separated by 1.0 µM TTX applied. Data are expressed as mean ± SD, *P < 0.05 and **P < 0.01 vs TTX-S in 50 mM Na+, ## P < 0.01 vs TTX-R in 150 mM Na+.
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Figure 2: The current density of TTX-S and TTX-R Na+ channels functionally expressed in low extracellular Na+ (50 mM Na+) and physiological extracellular Na+ environment. TTX-S Na+ currents (n = 7 for 50 mM Na+ and n = 8 for 150 mM Na+) were recorded from the VAN expressed TTX-S Na+ channel only; TTX-R Na+ currents (n = 34 for 50 mM Na+ and n = 21 for 150 mM Na+) were recorded from the VAN co-expressed TTX-S and TTX-R Na+ channel; and persistent TTX-R Na+ currents (n = 9) were recorded from the VAN co-expressed TTX-S, TTX-R, and persistent TTX-R Na+. TTX-R Na+ currents were separated by 1.0 µM TTX applied. Data are expressed as mean ± SD, *P < 0.05 and **P < 0.01 vs TTX-S in 50 mM Na+, ## P < 0.01 vs TTX-R in 150 mM Na+.

Mentions: Whole-cell Na+ current were recorded in different extracellular concentration of Na+. In 50 mM of Na+ recording medium (data not shown), 41 VANs were observed. 7 of them functionally expressed TTX-S Na+ currents and the rests were functionally expressed both TTX-S and TTX-R Na+ currents. Those VANs only expressed TTX-S Na+ currents are traditionally classified into myelinated A-types, whereas those VANs expressed both TTX-S and TTX-R Na+ channels were generally classified into unmyelinated C-types 6. However, recent study showed that a unique subset of myelinated Ah-type VANs with lower discharge threshold and higher repetitive discharge frequency were observed to not only express TTX-S but also TTX-R Na+ channels 6,7. None of tested VANs showed persistent TTX-R Na+ currents. These data are consistent with our previous report 3. Interestingly, as we increased extracellular Na+ concentration up to physiological concentration (150 mM Na+), 8 (~21%) out of 38 VANs only expressed TTX-S Na+ currents (Fig. 1A), 21 VANs expressed both TTX-S and TTX-R Na+ currents (Fig. 1B), and 9 (~23%) out of total 38 VANs functionally expressed persistent TTX-R Na+ currents except for TTX-S and TTX-R (Fig. 1C) without any treatment. The current density of either TTX-S Na+ currents in traditional A-types and TTX-R Na+ currents in traditional C-type VANs were increased by about 25% in the extracellular solution contained 150 mM of Na+ compared with that recorded from the recording medium with low extracellular Na+ (50 mM Na+), whereas the current density of VANs co-expressed persistent TTX-R Na+ currents were at least twice larger than that of C-types expressing TTX-S and TTX-R Na+ currents (Fig. 2). These results implied that the VANs co-expressed persistent TTX-R Na+ currents could have a lower discharge threshold, faster depolarization rate, and higher discharge frequency. Our recent report showed a perfect match that a subset of myelinated Ah-type VANs did possessed lower firing threshold and faster up-stroke velocity with significantly higher action potential firing frequency compared with C-type unmyelinated VANs 7.


Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents.

Qiao GF, Li BY, Zhou YH, Lu YJ, Schild JH - Int. J. Biol. Sci. (2009)

The current density of TTX-S and TTX-R Na+ channels functionally expressed in low extracellular Na+ (50 mM Na+) and physiological extracellular Na+ environment. TTX-S Na+ currents (n = 7 for 50 mM Na+ and n = 8 for 150 mM Na+) were recorded from the VAN expressed TTX-S Na+ channel only; TTX-R Na+ currents (n = 34 for 50 mM Na+ and n = 21 for 150 mM Na+) were recorded from the VAN co-expressed TTX-S and TTX-R Na+ channel; and persistent TTX-R Na+ currents (n = 9) were recorded from the VAN co-expressed TTX-S, TTX-R, and persistent TTX-R Na+. TTX-R Na+ currents were separated by 1.0 µM TTX applied. Data are expressed as mean ± SD, *P < 0.05 and **P < 0.01 vs TTX-S in 50 mM Na+, ## P < 0.01 vs TTX-R in 150 mM Na+.
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Figure 2: The current density of TTX-S and TTX-R Na+ channels functionally expressed in low extracellular Na+ (50 mM Na+) and physiological extracellular Na+ environment. TTX-S Na+ currents (n = 7 for 50 mM Na+ and n = 8 for 150 mM Na+) were recorded from the VAN expressed TTX-S Na+ channel only; TTX-R Na+ currents (n = 34 for 50 mM Na+ and n = 21 for 150 mM Na+) were recorded from the VAN co-expressed TTX-S and TTX-R Na+ channel; and persistent TTX-R Na+ currents (n = 9) were recorded from the VAN co-expressed TTX-S, TTX-R, and persistent TTX-R Na+. TTX-R Na+ currents were separated by 1.0 µM TTX applied. Data are expressed as mean ± SD, *P < 0.05 and **P < 0.01 vs TTX-S in 50 mM Na+, ## P < 0.01 vs TTX-R in 150 mM Na+.
Mentions: Whole-cell Na+ current were recorded in different extracellular concentration of Na+. In 50 mM of Na+ recording medium (data not shown), 41 VANs were observed. 7 of them functionally expressed TTX-S Na+ currents and the rests were functionally expressed both TTX-S and TTX-R Na+ currents. Those VANs only expressed TTX-S Na+ currents are traditionally classified into myelinated A-types, whereas those VANs expressed both TTX-S and TTX-R Na+ channels were generally classified into unmyelinated C-types 6. However, recent study showed that a unique subset of myelinated Ah-type VANs with lower discharge threshold and higher repetitive discharge frequency were observed to not only express TTX-S but also TTX-R Na+ channels 6,7. None of tested VANs showed persistent TTX-R Na+ currents. These data are consistent with our previous report 3. Interestingly, as we increased extracellular Na+ concentration up to physiological concentration (150 mM Na+), 8 (~21%) out of 38 VANs only expressed TTX-S Na+ currents (Fig. 1A), 21 VANs expressed both TTX-S and TTX-R Na+ currents (Fig. 1B), and 9 (~23%) out of total 38 VANs functionally expressed persistent TTX-R Na+ currents except for TTX-S and TTX-R (Fig. 1C) without any treatment. The current density of either TTX-S Na+ currents in traditional A-types and TTX-R Na+ currents in traditional C-type VANs were increased by about 25% in the extracellular solution contained 150 mM of Na+ compared with that recorded from the recording medium with low extracellular Na+ (50 mM Na+), whereas the current density of VANs co-expressed persistent TTX-R Na+ currents were at least twice larger than that of C-types expressing TTX-S and TTX-R Na+ currents (Fig. 2). These results implied that the VANs co-expressed persistent TTX-R Na+ currents could have a lower discharge threshold, faster depolarization rate, and higher discharge frequency. Our recent report showed a perfect match that a subset of myelinated Ah-type VANs did possessed lower firing threshold and faster up-stroke velocity with significantly higher action potential firing frequency compared with C-type unmyelinated VANs 7.

Bottom Line: The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9.Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV).These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.

ABSTRACT
Persistent tetrodotoxin-resistant (TTX-R) Na(+) (Na(v)1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na(+) although the functional expression of this current was observed in the presence of PGE(2) or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na(+)). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na(+) currents were expressed in 9 out of 38 VANs bathed in 150 mM Na(+). The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV). This indicates that persistent TTX-R Na(+) channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

Show MeSH
Related in: MedlinePlus