Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats

Shawn G. Hayes, Angela E. Kindig, Marc P Kaufman

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage-gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 μg kg-1; I.A.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 μg kg-1, I.A.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 μg kg-1) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 μg kg-1) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.

Original languageEnglish (US)
Pages (from-to)1271-1282
Number of pages12
JournalJournal of Physiology
Volume581
Issue number3
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Physiology

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