scholarly journals Ionic mechanisms underlying the negative chronotropic action of propofol on sinoatrial node automaticity in guinea pig heart

2014 ◽  
Vol 172 (3) ◽  
pp. 799-814 ◽  
Author(s):  
Akiko Kojima ◽  
Yuki Ito ◽  
Hirotoshi Kitagawa ◽  
Hiroshi Matsuura
2013 ◽  
Vol 117 (5) ◽  
pp. 1072-1077 ◽  
Author(s):  
Akiko Kojima ◽  
Yuki Ito ◽  
Hirotoshi Kitagawa ◽  
Hiroshi Matsuura ◽  
Shuichi Nosaka

2014 ◽  
Vol 120 (6) ◽  
pp. 1400-1413 ◽  
Author(s):  
Akiko Kojima ◽  
Yuki Ito ◽  
Hirotoshi Kitagawa ◽  
Hiroshi Matsuura ◽  
Shuichi Nosaka

Abstract Background: Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Methods: Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), Na+/Ca2+ exchange current (INCX), and rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Results: Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Conclusions: Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.


2012 ◽  
Vol 166 (7) ◽  
pp. 2117-2135 ◽  
Author(s):  
Akiko Kojima ◽  
Hirotoshi Kitagawa ◽  
Mariko Omatsu-Kanbe ◽  
Hiroshi Matsuura ◽  
Shuichi Nosaka

Author(s):  
W. Allen Shannon ◽  
Hannah L. Wasserkrug ◽  
andArnold M. Seligman

The synthesis of a new substrate, p-N,N-dimethylamino-β-phenethylamine (DAPA)3 (Fig. 1) (1,2), and the testing of it as a possible substrate for tissue amine oxidase activity have resulted in the ultracytochemical localization of enzyme oxidase activity referred to as DAPA oxidase (DAPAO). DAPA was designed with the goal of providing an amine that would yield on oxidation a stronger reducing aldehyde than does tryptamine in the histochemical demonstration of monoamine oxidase (MAO) with tetrazolium salts.Ultracytochemical preparations of guinea pig heart, liver and kidney and rat heart and liver were studied. Guinea pig kidney, known to exhibit high levels of MAO, appeared the most reactive of the tissues studied. DAPAO reaction product appears primarily in mitochondrial outer compartments and cristae (Figs. 2-4). Reaction product is also localized in endoplasmic reticulum, cytoplasmic vacuoles and nuclear envelopes (Figs. 2 and 3) and in the sarcoplasmic reticulum of heart.


2002 ◽  
Vol 80 (6) ◽  
pp. 578-587 ◽  
Author(s):  
María de Jesús Gómez ◽  
Guy Rousseau ◽  
Réginald Nadeau ◽  
Roberto Berra ◽  
Gonzalo Flores ◽  
...  

Dopamine receptors include the D1- (D1 and D5 subtypes) and D2-like (D2, D3, and D4 subtypes) families. D1-like receptors are positively and D2-like receptors negatively coupled to the adenylyl cyclase. Dopamine D2-like (D4 subtype) receptors have been identified in human and rat hearts. However the presence of D2 and D3 receptor subtypes is unclear. Furthermore, their role in cardiac functions is unknown. By autoradiographic studies of guinea pig hearts, we identified D3 and D4 receptors, using the selective radioligands [3H]-7-OH-DPAT and [3H]emonapride (YM-09151-2 plus raclopride). Western blot analysis confirmed D3 and D4 receptors in the right and left ventricle of the same species. Selective agonists of D3 and D4 receptors (±)-7-OH-DPAT and PD 168 077 (10–9 to 10–5 M, respectively) induced a significant negative chronotropic and inotropic effect in the isolated guinea pig heart preparation. Negative inotropic effect induced by PD 168 077 was associated with an inhibition in cyclase activity. No changes in cyclase activity were found with (±)-7-OH-DPAT. The aim of this study is to support the presence of D3 and D4 receptors in the heart. Although our results suggest that D3 and D4 receptors are functionally active in the heart, we need additional information with an antagonist and an agonist of improved potency and selectivity to understand the respective roles of D3 and D4 receptors in the cardiac functions.Key words: Dopamine receptors (D2, D3, D4 subtypes), autoradiography, Western blot, cAMP, heart.


Sign in / Sign up

Export Citation Format

Share Document