Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats

Stefan Schwarz, Wolfgang Greffrath, Dietrich Busselberg, Rolf Detlef Treede

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

1. Membrane currents evoked by repeated noxious heat stimuli (43-47°C) of 3 s duration were investigated in acutely dissociated dorsal root ganglion (DRG) neurones of adult rats. The heat stimuli generated by a fast solution exchanger had a rise time of 114±6 ms and a fall time of 146±13 ms. 2. When heat stimuli were applied to heat-sensitive small (≤ 32.5 μm) DRG neurones, an inward membrane current (I(heat)) with a mean peak of 2430 ± 550 pA was observed (n = 19). This current started to activate and deactivate with no significant latency with respect to the heat stimulus. The peak of I(heat) was reached with a rise time of 625 ± 115 ms. When the heat stimulus was switched off I(heat) deactivated with a fall time of 263 ± 17 ms. 3. During constant heat stimulation I(heat) decreased with time constants of 4-5 s (inactivation). At the end of a 3 s heat stimulus the peak current was reduced by 44 ± 5% (n = 19). 4. Current-voltage curves revealed outward rectifying properties of I(heat) and a reversal potential of -6.3 ± 2.2 mV (n = 6). Inactivation was observed at all membrane potentials investigated (-80 to 60 mV); however, inactivation was more pronounced for inward currents (37 ± 5%) than for outward currents (23 ± 6%, P < 0·05). 5. When neurones were investigated with repeated heat stimuli (3 to 5 times) of the same temperature, the peak current relative to the first I(heat) declined by 48 ± 6% at the 3rd stimulus (n = 19) and by 54 ± 18% at the 5th stimulus (n = 4; tachyphylaxis). 6. In the absence of extracellular Ca2+ (buffered with 10 mM EGTA) inactivation (by 53 ± 6%) and tachyphylaxis (by 42 ± 7% across three stimuli) were still observed (n = 8). The same was true when intracellular Ca2+ was buffered by 10 mM BAPTA (inactivation by 49 ± 4%, tachyphylaxis by 52 ± 7% across three stimuli; n = 13). Thus, inactivation and tachyphylaxis were mainly independent of intra- and extracellular Ca2+. 7. These results indicate that inactivation and tachyphylaxis of heat-evoked inward currents can be observed in vitro, similar to adaptation and suppression of action potential discharges elicited by comparably fast heat stimuli in vivo. Whereas the voltage dependence of I(heat) resembles that of capsaicin-induced membrane currents (I(Caps)), the independence of inactivation and tachyphylaxis of I(heat) from calcium is in clear contrast to I(Caps). A similar difference in calcium dependence of inactivation has been reported between heat-evoked and capsaicin-induced currents through the cloned capsaicin receptor channel VR1. Thus, the properties of I(heat) and of VR1 largely account for the adaptation and suppression of heat-evoked nociceptor discharges.

Original languageEnglish
Pages (from-to)539-549
Number of pages11
JournalJournal of Physiology
Volume528
Issue number3
Publication statusPublished - 1 Nov 2000
Externally publishedYes

Fingerprint

Tachyphylaxis
Sensory Receptor Cells
Hot Temperature
Capsaicin
Spinal Ganglia
Neurons
Membranes

ASJC Scopus subject areas

  • Physiology

Cite this

Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats. / Schwarz, Stefan; Greffrath, Wolfgang; Busselberg, Dietrich; Treede, Rolf Detlef.

In: Journal of Physiology, Vol. 528, No. 3, 01.11.2000, p. 539-549.

Research output: Contribution to journalArticle

Schwarz, Stefan ; Greffrath, Wolfgang ; Busselberg, Dietrich ; Treede, Rolf Detlef. / Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats. In: Journal of Physiology. 2000 ; Vol. 528, No. 3. pp. 539-549.
@article{a99f99449e32418db999b2fd3da4f4eb,
title = "Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats",
abstract = "1. Membrane currents evoked by repeated noxious heat stimuli (43-47°C) of 3 s duration were investigated in acutely dissociated dorsal root ganglion (DRG) neurones of adult rats. The heat stimuli generated by a fast solution exchanger had a rise time of 114±6 ms and a fall time of 146±13 ms. 2. When heat stimuli were applied to heat-sensitive small (≤ 32.5 μm) DRG neurones, an inward membrane current (I(heat)) with a mean peak of 2430 ± 550 pA was observed (n = 19). This current started to activate and deactivate with no significant latency with respect to the heat stimulus. The peak of I(heat) was reached with a rise time of 625 ± 115 ms. When the heat stimulus was switched off I(heat) deactivated with a fall time of 263 ± 17 ms. 3. During constant heat stimulation I(heat) decreased with time constants of 4-5 s (inactivation). At the end of a 3 s heat stimulus the peak current was reduced by 44 ± 5{\%} (n = 19). 4. Current-voltage curves revealed outward rectifying properties of I(heat) and a reversal potential of -6.3 ± 2.2 mV (n = 6). Inactivation was observed at all membrane potentials investigated (-80 to 60 mV); however, inactivation was more pronounced for inward currents (37 ± 5{\%}) than for outward currents (23 ± 6{\%}, P < 0·05). 5. When neurones were investigated with repeated heat stimuli (3 to 5 times) of the same temperature, the peak current relative to the first I(heat) declined by 48 ± 6{\%} at the 3rd stimulus (n = 19) and by 54 ± 18{\%} at the 5th stimulus (n = 4; tachyphylaxis). 6. In the absence of extracellular Ca2+ (buffered with 10 mM EGTA) inactivation (by 53 ± 6{\%}) and tachyphylaxis (by 42 ± 7{\%} across three stimuli) were still observed (n = 8). The same was true when intracellular Ca2+ was buffered by 10 mM BAPTA (inactivation by 49 ± 4{\%}, tachyphylaxis by 52 ± 7{\%} across three stimuli; n = 13). Thus, inactivation and tachyphylaxis were mainly independent of intra- and extracellular Ca2+. 7. These results indicate that inactivation and tachyphylaxis of heat-evoked inward currents can be observed in vitro, similar to adaptation and suppression of action potential discharges elicited by comparably fast heat stimuli in vivo. Whereas the voltage dependence of I(heat) resembles that of capsaicin-induced membrane currents (I(Caps)), the independence of inactivation and tachyphylaxis of I(heat) from calcium is in clear contrast to I(Caps). A similar difference in calcium dependence of inactivation has been reported between heat-evoked and capsaicin-induced currents through the cloned capsaicin receptor channel VR1. Thus, the properties of I(heat) and of VR1 largely account for the adaptation and suppression of heat-evoked nociceptor discharges.",
author = "Stefan Schwarz and Wolfgang Greffrath and Dietrich Busselberg and Treede, {Rolf Detlef}",
year = "2000",
month = "11",
day = "1",
language = "English",
volume = "528",
pages = "539--549",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats

AU - Schwarz, Stefan

AU - Greffrath, Wolfgang

AU - Busselberg, Dietrich

AU - Treede, Rolf Detlef

PY - 2000/11/1

Y1 - 2000/11/1

N2 - 1. Membrane currents evoked by repeated noxious heat stimuli (43-47°C) of 3 s duration were investigated in acutely dissociated dorsal root ganglion (DRG) neurones of adult rats. The heat stimuli generated by a fast solution exchanger had a rise time of 114±6 ms and a fall time of 146±13 ms. 2. When heat stimuli were applied to heat-sensitive small (≤ 32.5 μm) DRG neurones, an inward membrane current (I(heat)) with a mean peak of 2430 ± 550 pA was observed (n = 19). This current started to activate and deactivate with no significant latency with respect to the heat stimulus. The peak of I(heat) was reached with a rise time of 625 ± 115 ms. When the heat stimulus was switched off I(heat) deactivated with a fall time of 263 ± 17 ms. 3. During constant heat stimulation I(heat) decreased with time constants of 4-5 s (inactivation). At the end of a 3 s heat stimulus the peak current was reduced by 44 ± 5% (n = 19). 4. Current-voltage curves revealed outward rectifying properties of I(heat) and a reversal potential of -6.3 ± 2.2 mV (n = 6). Inactivation was observed at all membrane potentials investigated (-80 to 60 mV); however, inactivation was more pronounced for inward currents (37 ± 5%) than for outward currents (23 ± 6%, P < 0·05). 5. When neurones were investigated with repeated heat stimuli (3 to 5 times) of the same temperature, the peak current relative to the first I(heat) declined by 48 ± 6% at the 3rd stimulus (n = 19) and by 54 ± 18% at the 5th stimulus (n = 4; tachyphylaxis). 6. In the absence of extracellular Ca2+ (buffered with 10 mM EGTA) inactivation (by 53 ± 6%) and tachyphylaxis (by 42 ± 7% across three stimuli) were still observed (n = 8). The same was true when intracellular Ca2+ was buffered by 10 mM BAPTA (inactivation by 49 ± 4%, tachyphylaxis by 52 ± 7% across three stimuli; n = 13). Thus, inactivation and tachyphylaxis were mainly independent of intra- and extracellular Ca2+. 7. These results indicate that inactivation and tachyphylaxis of heat-evoked inward currents can be observed in vitro, similar to adaptation and suppression of action potential discharges elicited by comparably fast heat stimuli in vivo. Whereas the voltage dependence of I(heat) resembles that of capsaicin-induced membrane currents (I(Caps)), the independence of inactivation and tachyphylaxis of I(heat) from calcium is in clear contrast to I(Caps). A similar difference in calcium dependence of inactivation has been reported between heat-evoked and capsaicin-induced currents through the cloned capsaicin receptor channel VR1. Thus, the properties of I(heat) and of VR1 largely account for the adaptation and suppression of heat-evoked nociceptor discharges.

AB - 1. Membrane currents evoked by repeated noxious heat stimuli (43-47°C) of 3 s duration were investigated in acutely dissociated dorsal root ganglion (DRG) neurones of adult rats. The heat stimuli generated by a fast solution exchanger had a rise time of 114±6 ms and a fall time of 146±13 ms. 2. When heat stimuli were applied to heat-sensitive small (≤ 32.5 μm) DRG neurones, an inward membrane current (I(heat)) with a mean peak of 2430 ± 550 pA was observed (n = 19). This current started to activate and deactivate with no significant latency with respect to the heat stimulus. The peak of I(heat) was reached with a rise time of 625 ± 115 ms. When the heat stimulus was switched off I(heat) deactivated with a fall time of 263 ± 17 ms. 3. During constant heat stimulation I(heat) decreased with time constants of 4-5 s (inactivation). At the end of a 3 s heat stimulus the peak current was reduced by 44 ± 5% (n = 19). 4. Current-voltage curves revealed outward rectifying properties of I(heat) and a reversal potential of -6.3 ± 2.2 mV (n = 6). Inactivation was observed at all membrane potentials investigated (-80 to 60 mV); however, inactivation was more pronounced for inward currents (37 ± 5%) than for outward currents (23 ± 6%, P < 0·05). 5. When neurones were investigated with repeated heat stimuli (3 to 5 times) of the same temperature, the peak current relative to the first I(heat) declined by 48 ± 6% at the 3rd stimulus (n = 19) and by 54 ± 18% at the 5th stimulus (n = 4; tachyphylaxis). 6. In the absence of extracellular Ca2+ (buffered with 10 mM EGTA) inactivation (by 53 ± 6%) and tachyphylaxis (by 42 ± 7% across three stimuli) were still observed (n = 8). The same was true when intracellular Ca2+ was buffered by 10 mM BAPTA (inactivation by 49 ± 4%, tachyphylaxis by 52 ± 7% across three stimuli; n = 13). Thus, inactivation and tachyphylaxis were mainly independent of intra- and extracellular Ca2+. 7. These results indicate that inactivation and tachyphylaxis of heat-evoked inward currents can be observed in vitro, similar to adaptation and suppression of action potential discharges elicited by comparably fast heat stimuli in vivo. Whereas the voltage dependence of I(heat) resembles that of capsaicin-induced membrane currents (I(Caps)), the independence of inactivation and tachyphylaxis of I(heat) from calcium is in clear contrast to I(Caps). A similar difference in calcium dependence of inactivation has been reported between heat-evoked and capsaicin-induced currents through the cloned capsaicin receptor channel VR1. Thus, the properties of I(heat) and of VR1 largely account for the adaptation and suppression of heat-evoked nociceptor discharges.

UR - http://www.scopus.com/inward/record.url?scp=0034325893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034325893&partnerID=8YFLogxK

M3 - Article

C2 - 11060130

AN - SCOPUS:0034325893

VL - 528

SP - 539

EP - 549

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 3

ER -