Acetylcholine Modulates Ifand IK(ACh)Via Different Pathways in Rabbit Sino-atrial Node Cells

Renaudon, Barbara; Bois, Patrick; Bescond, Jocelyn; Lenfant, J

doi:10.1006/jmcc.1996.0340

Cited by 22 publications

(17 citation statements)

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“…As the frequency components of the heart rate spectra are affected by both sympathetic and parasympathetic nervous systems inputs, HRV analysis allows quantification of their respective contributions. We found that the direct, membrane-delimited activation of K ACh is important for beat-to-beat modulation of heart rate by the autonomic nervous system, which functions on a second time scale, in contrast to the involvement of a second messenger system (cAMP) operating on a tens-of-seconds time scale (25).…”

Section: Discussionmentioning

confidence: 86%

“…In the sinoatrial node, most of the basal K ϩ conductance is due to K ACh , and in pacemaker cells any changes in its activity can alter excitability and heart rate (11). Second, in addition to K ACh , ACh modulates the pacemaker current (I f ) in sinoatrial nodal cells (25,36). There are some important differences between I f and K ACh modulation.…”

Section: Discussionmentioning

confidence: 99%

“…Heart rate control by inhibition of I f is achieved with moderate vagal stimulation or low doses of ACh, whereas stronger vagal activity or a higher concentration of ACh is required for greater bradycardia due to activation of K ACh (7). Furthermore, I f regulation by muscarinic receptors is mediated by a second messenger (cAMP) and not by direct activation through G␤␥ (25). Our data implicate alterations in K ACh regulation as the major underlying mechanism, because diminution in I f should have caused abnormalities in heart rate in transgenic mice under baseline conditions, (i.e., before muscarinic stimulation) and, in addition, prevention of vagal-provoked atrial fibrillation would have been unlikely.…”

Section: Discussionmentioning

confidence: 99%

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Impaired parasympathetic heart rate control in mice with a reduction of functional G protein βγ-subunits

Gehrmann¹,

Meister

Maguire³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Impaired parasympathetic heart rate control in mice with a reduction of functional G protein ␤␥-subunits. Am J Physiol Heart Circ Physiol 282: H445-H456, 2002; 10.1152/ajpheart. 00565.2001.-Acetylcholine released on parasympathetic stimulation slows heart rate through activation of muscarinic receptors on the sinus nodal cells and subsequent opening of the atrial muscarinic potassium channel (K ACh). KACh is directly activated by G protein ␤␥-subunits. To elucidate the physiological role of G␤␥ for the regulation of heart rate and electrophysiological function in vivo, we created transgenic mice with a reduced amount of membrane-bound G␤ protein by overexpressing nonprenylated G␥ 2-subunits in their hearts using the ␣-myosin heavy chain promoter. At baseline and after muscarinic stimulation with carbachol, heart rate and heart rate variability were determined with electrocardiogram telemetry in conscious mice and in vivo intracardiac electrophysiological studies in anesthetized mice. Reduction of the amount of functional G␤␥ protein by Ͼ50% caused a pronounced blunting of the carbachol-induced bradycardia as well as the increases in time-and frequency-domain indexes of heart rate variability and baroreflex sensitivity that were observed in wild types. In addition, sinus node recovery time and inducibility of atrial arrhythmias were reduced in transgenic mice. Our data demonstrate in vivo that G␤␥ plays a crucial role for parasympathetic heart rate control, sinus node automaticity, and atrial arrhythmia vulnerability. atrial arrhythmia; heart rate regulation; in vivo electrophysiology; sinus node pacemaker activity; transgenic mice SINOATRIAL NODAL CELLS of the heart are characterized by slow and spontaneous diastolic depolarization, which is the basis of their pacemaking activity (11). The inwardly rectifying potassium channel (K ACh ) in the pacemaker cells of the sinoatrial node is an important ionic mechanism that underlies modulation of the chronotropic properties in the heart under vagal stimulation. ACh released on vagal stimulation slows the heart rate through activation of muscarinic receptors and subsequent opening of K ACh . This process is in part mediated by hyperpolarization of pacemaker cells due to increased potassium conductance of the membrane. K ACh is of clinical significance, because it plays an important part in determining the atrial resting membrane potential and the shape of the cardiac action potential during the final phase of repolarization. K ACh opens primarily near the resting potential but closes at depolarized membrane potentials. Impaired activation can therefore decrease the excitation threshold and lead to premature generation of the action potential. In addition, it is the major effector of parasympathetic signal transduction in atrial myocytes.I KACh is present in the sinoatrial node, atria, atrioventricular node, and possibly Purkinje fibers of the mammalian heart (27). The cloning of GIRK1 and GIRK4, which constitute cardiac inward rectifier potassium channels by forming...

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Impaired parasympathetic heart rate control in mice with a reduction of functional G protein βγ-subunits

Gehrmann¹,

Meister

Maguire³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

mentioning

confidence: 99%

“…Published data show that parasympathetic regulatory influences on the heart are realized via muscarinic M 2 AChR [10]. Recent studies indicate that muscarinic M 1 and M 3 AChR play a role in cholinergic regulatory influences on the heart [4,11,13,14].Study of vagal regulation of the heart in laboratory animals revealed significant interstrain differences in the mechanisms of cardiac rhythm regulation in rats [1,3,7]. The possibility of immediate and tonic vagal inhibition of cardiac activity in rats was hypothesized [2].…”

mentioning

confidence: 99%

Cardiac activity and blood pressure in rats during selective blockade of various subtypes of muscarinic cholinoceptors

et al. 2006

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Cardiac activity and blood pressure in adult rats were recorded during selective blockade of cholinoceptors. Blockade of muscarinic M1 and M2-cholinoceptors had little effect on cardiac activity. Blockade of muscarinic M3-cholinoceptors was followed by heart acceleration. The data suggest that the tonic inhibitory influence of the vagus nerve is mediated via cardiac muscarinic M3-cholinoceptors. Electrostimulation of the right vagus nerve during selective blockade of various subtypes of muscarinic cholinoceptors was followed by the decrease in heart rate. Our results indicate that muscarinic cholinoceptors play a role in the immediate inhibition of cardiac activity upon vagus nerve stimulation.

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Human Cardiovascular Responses to Passive Heat Stress

Crandall

Wilson

2014

Comprehensive Physiology

153

136

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Heat stress increases human morbidity and mortality compared to normothermic conditions. Many occupations, disease states, as well as stages of life are especially vulnerable to the stress imposed on the cardiovascular system during exposure to hot ambient conditions. This review focuses on the cardiovascular responses to heat stress that are necessary for heat dissipation. To accomplish this regulatory feat requires complex autonomic nervous system control of the heart and various vascular beds. For example, during heat stress cardiac output increases up to twofold, by increases in heart rate and an active maintenance of stroke volume via increases in inotropy in the presence of decreases in cardiac preload. Baroreflexes retain the ability to regulate blood pressure in many, but not all, heat stress conditions. Central hypovolemia is another cardiovascular challenge brought about by heat stress, which if added to a subsequent central volumetric stress, such as hemorrhage, can be problematic and potentially dangerous, as syncope and cardiovascular collapse may ensue. These combined stresses can compromise blood flow and oxygenation to important tissues such as the brain. It is notable that this compromised condition can occur at cardiac outputs that are adequate during normothermic conditions but are inadequate in heat because of the increased systemic vascular conductance associated with cutaneous vasodilation. Understanding the mechanisms within this complex regulatory system will allow for the development of treatment recommendations and countermeasures to reduce risks during the ever-increasing frequency of severe heat events that are predicted to occur.

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Acetylcholine Modulates Ifand IK(ACh)Via Different Pathways in Rabbit Sino-atrial Node Cells

Cited by 22 publications

References 0 publications

Impaired parasympathetic heart rate control in mice with a reduction of functional G protein βγ-subunits

Impaired parasympathetic heart rate control in mice with a reduction of functional G protein βγ-subunits

Cardiac activity and blood pressure in rats during selective blockade of various subtypes of muscarinic cholinoceptors

Human Cardiovascular Responses to Passive Heat Stress

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