Abstract
Atropine is commonly used to counter the effects of the parasympathetic neurotransmitter acetylcholine on heart rate in clinical practice, such as in the perioperative period; however, individual differences in the response to atropine are huge. The association between SCN10A/voltage-gated sodium channel 1.8 (NaV1.8) and cardiac conduction has been demonstrated; however, the exact role of SCN10A/NaV1.8 in the heart rate response to atropine remains unclear. To identify the role of SCN10A variants that influence the heart rate responses to atropine, we carried out a retrospective study in 1,005 Han Chinese subjects. Our results showed that rs6795970 was associated with the heart rate response to atropine. The heart rate responses to atropine and methoctramine in NaV1.8 knockout mice were lower, whereas the heart rate response to isoproterenol was like those in wild type mice. Furthermore, we observed that the NaV1.8 blocker A-803467 alleviated the heart rate response to atropine in wild type mice. The retrospective study revealed a previously unknown role of NaV1.8 in controlling the heart rate response to atropine, as shown by the animal study, a speculative mechanism that may involve the cardiac muscarinic acetylcholine receptor M2.
Highlights
Atropine is a competitive antagonist of acetylcholine muscarinic receptors because of its similar structure with acetylcholine, a parasympathetic neurotransmitter (Lakstygal et al, 2019)
This study indicated that a patient’s response to atropine may be affected by different SCN10A rs6795970 alleles (G>A; p.Ala1073Val)
The SCN10A variant rs6795970 was associated with heart rate response to atropine in the human population
Summary
Atropine is a competitive antagonist of acetylcholine muscarinic receptors because of its similar structure with acetylcholine, a parasympathetic neurotransmitter (Lakstygal et al, 2019). An increase in parasympathetic activity can lead to transient bradycardia and even to asystole, which can affect cerebral oxygenation and perfusion (Rasmussen et al, 2007; Anastasian et al, 2014). Atropine is commonly used to counter the effects of acetylcholine on heart rate and rapidly increase the heart rate of patients with bradycardia in clinical practice, such as during the perioperative period. Nav1.8 Affects Atropine Response to atropine (Lee et al, 2008); the atropine test is often used to evaluate the sensitivity of the individual to atropine. The mechanism underlying the differences in atropine sensitivity among individuals is unclear. The exploration of a mechanism will elucidate the individual variation to atropine and may provide a new target for clinical heart rate intervention
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