Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

The automaticity of the pulmonary vein myocardium is known to be the major cause of atrial fibrillation. We examined the involvement of angiotensin II in the automatic activity of isolated guinea pig pulmonary vein preparations. In tissue preparations, application of angiotensin II induced an automatic contractile activity; this effect was mimicked by angiotensin I and blocked by losartan, but not by PD123,319 or carvedilol. In cardiomyocytes, application of angiotensin II induced an increase in the frequency of spontaneous Ca2+ sparks and the generation of Ca2+ transients; these effects were inhibited by losartan or xestospongin C. In tissue preparations, angiotensin II caused membrane potential oscillations, which lead to repetitive generation of action potentials. Angiotensin II increased the diastolic depolarization slope of the spontaneous or evoked action potentials. These effects of angiotensin II were inhibited by SEA0400. In tissue preparations showing spontaneous firing of action potentials, losartan, xestospongin C or SEA0400 decreased the slope of the diastolic depolarization and inhibited the firing of action potentials. In conclusion, in the guinea pig pulmonary vein myocardium, angiotensin II induces the generation of automatic activity through activation of the IP3 receptor and the Na+-Ca2+ exchanger.

Download Full-text

Involvement of the persistent Na+ current in the diastolic depolarization and automaticity of the guinea pig pulmonary vein myocardium

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2019.08.003 ◽

2019 ◽

Vol 141 (1) ◽

pp. 9-16 ◽

Cited By ~ 1

Author(s):

Masahiko Irie ◽

Haruhito Hiiro ◽

Shogo Hamaguchi ◽

Iyuki Namekata ◽

Hikaru Tanaka

Keyword(s):

Guinea Pig ◽

Pulmonary Vein ◽

Na Current ◽

Diastolic Depolarization

Download Full-text

Membrane potential oscillations in molluscan “burster” neurones

Journal of Experimental Biology ◽

10.1242/jeb.81.1.93 ◽

1979 ◽

Vol 81 (1) ◽

pp. 93-112

Author(s):

R. W. Meech

Keyword(s):

Membrane Potential ◽

Action Potential ◽

Intracellular Ph ◽

Action Potentials ◽

Outward Current ◽

Ionized Calcium ◽

Isolated Cells ◽

Potential Oscillations ◽

Inward Current ◽

Membrane Potential Oscillations

Membrane potential oscillations can be induced in molluscan neurones under a variety of artificial conditions. In the so-called ‘burster’ neurones oscillations are generated even in isolated cells. A likely mechanism for ‘bursting’ involves the following ionic currents: 1. A transient inward current carried by Na+ and Ca2+. This current is responsible for the upstroke of the action potentials. 2. A delayed outward current carried by K+. This current is voltage-sensitive and is responsible for the downstroke of the action potential during the early part of the burst. It becomes progressively inactivated during the burst. Its amplitude depends on the intracellular pH. 3. A rapidly developing outward current carried by K+ which is inactivated at potentials close to action potential threshold. This current tends to hold the membrane in the hyperpolarized state and is involved in spacing the action potentials. 4. A prolonged inward current which may not inactivate. It is probably carried by both Na+ and Ca2+. This current is responsible for the depolarizing phase of the burst but also contributes to the action potential. 5. A slowly developing outward current, carried by K+. This current appears as a result of a slow increase in intracellular ionized calcium and is responsible for the hyperpolarizing phase of the burst. Note that a transient increase in this current may also contribute to the falling phase of the action potential during the later stages of the burst. It is also sensitive to intracellular pH. One of the more significant features of this system of producing membrane potential oscillations is that the frequency of the bursts depends on the rate at which the intracellular ionized calcium returns to its resting level. This process depends on the metabolic state of the animal which can thereby exert a considerable influence on the electrical activity of burster neurones.

Download Full-text

The myogenic component in distention-induced peristalsis in the guinea pig small intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.280.3.g491 ◽

2001 ◽

Vol 280 (3) ◽

pp. G491-G500 ◽

Cited By ~ 16

Author(s):

Graeme Donnelly ◽

Timothy D. Jackson ◽

Krista Ambrous ◽

Jing Ye ◽

Adeel Safdar ◽

...

Keyword(s):

Small Intestine ◽

Guinea Pig ◽

Slow Wave ◽

Action Potentials ◽

Slow Waves ◽

Intraluminal Pressure ◽

Control Activity ◽

Potential Oscillations ◽

Frequency Gradient

In an in vitro model for distention-induced peristalsis in the guinea pig small intestine, the electrical activity, intraluminal pressure, and outflow of contents were studied simultaneously to search for evidence of myogenic control activity. Intraluminal distention induced periods of nifedipine-sensitive slow wave activity with superimposed action potentials, alternating with periods of quiescence. Slow waves and associated high intraluminal pressure transients propagated aborally, causing outflow of content. In the proximal small intestine, a frequency gradient of distention-induced slow waves was observed, with a frequency of 19 cycles/min in the first 1 cm and 11 cycles/min 10 cm distally. Intracellular recording revealed that the guinea pig small intestinal musculature, in response to carbachol, generated slow waves with superimposed action potentials, both sensitive to nifedipine. These slow waves also exhibited a frequency gradient. In addition, distention and cholinergic stimulation induced high-frequency membrane potential oscillations (∼55 cycles/min) that were not associated with distention-induced peristalsis. Continuous distention produced excitation of the musculature, in part neurally mediated, that resulted in periodic occurrence of bursts of distally propagating nifedipine-sensitive slow waves with superimposed action potentials associated with propagating intraluminal pressure waves that caused pulsatile outflow of content at the slow wave frequency.

Download Full-text

Intracellular calcium and membrane potential oscillations in the pulmonary vein myocardium

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.wcp2018.0_po3-3-42 ◽

2018 ◽

Vol WCP2018 (0) ◽

pp. PO3-3-42

Author(s):

Iyuki Namekata ◽

Masahiko Iie ◽

Haruna Kanae ◽

Yayoi Tsuneoka ◽

Shogo Hamaguchi ◽

...

Keyword(s):

Membrane Potential ◽

Intracellular Calcium ◽

Pulmonary Vein ◽

Potential Oscillations ◽

Membrane Potential Oscillations

Download Full-text

Differential effects of class I antiarrhythmic drugs on the guinea pig pulmonary vein myocardium: Inhibition of automatic activity correlates with blockade of a diastolic sodium current component

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2020.05.004 ◽

2020 ◽

Vol 143 (4) ◽

pp. 325-329

Author(s):

Masahiko Irie ◽

Haruhito Hiiro ◽

Shu Kato ◽

Mizuki Kuramochi ◽

Shogo Hamaguchi ◽

...

Keyword(s):

Guinea Pig ◽

Pulmonary Vein ◽

Antiarrhythmic Drugs ◽

Sodium Current ◽

Class I ◽

Current Component ◽

Differential Effects ◽

Automatic Activity

Download Full-text

Possible role of Na+–Ca2+ exchange in the regulation of contractility in isolated adult ventricular myocytes from rat and guinea pig

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-246 ◽

1989 ◽

Vol 67 (12) ◽

pp. 1525-1533 ◽

Cited By ~ 8

Author(s):

M. Horackova

Keyword(s):

Guinea Pig ◽

Action Potentials ◽

Ventricular Myocytes ◽

Contractile Activity ◽

Strong Dependence ◽

Tonic Component ◽

Adult Rat ◽

Phasic Component ◽

Single Ventricular Myocytes ◽

Rat Myocytes

Action potentials and developed contractions of externally unloaded single ventricular myocytes isolated from adult rat and guinea pig hearts were recorded by means of an optical system for recording contractile activity during regular stimulation by microelectrodes. Under control conditions, the shortenings (twitches) in the rat myocytes were fully inhibited by 0.1 μM ryanodine, but they were rather insensitive to the Ca2+ blocker 0.2–0.5 μM nifedipine. In contrast, the contractions of the isolated guinea pig ventricular myocytes were greatly suppressed by 0.2–0.5 μM nifedipine (to <30%), while they were only slightly reduced by 1 μM ryanodine. When the Na+ gradient was decreased by reducing [Na]o or by elevating [Na]i in the presence of veratridine, the twitch contractions were increased in both species. The effect of reduced [Na]o on twitch contractions was not affected by ryanodine in either type of myocytes, while nifedipine still fully abolished the twitches in the guinea pig cells, indicating a strong dependence of guinea pig contractions on Ca2+ influx. On the other hand, the effect of a reduced Na gradient by veratridine was more complex; the usual twitch (phasic component) was increased and it was followed by a second (tonic) component which relaxed only after the repolarization of the action potential. While the phasic component was decreased by nifedipine and ryanodine in the usual way (as in the controls), the sustained contractions (lasting up to several seconds) were ryanodine and nifedipine insensitive. Furthermore, the cardiomyocytes of both species exposed to strontium in place of external calcium still exhibited all the effects observed when reducing the Na+ gradient. These data indicated that Sr2+ transport may occur via various routes similar to those of Ca2+ transport, including the Na+–Sr2+ exchange. In addition, in the presence of SrCl2 the rat myocytes exhibited longer durations of action potentials and their contractions became insensitive to ryanodine (like the guinea pig cells). It is concluded that Na+–Ca2+ exchange probably does not directly contribute in a quantitative fashion to the activation of contractile activity under normal conditions, but when the Na+ gradient is decreased, especially by increasing [Na]i, the contractions could be increased severalfold via this mechanism in both the rat and guinea pig cardiomyocytes.Key words: excitation–contraction coupling, isolated cardiac myocytes, nifedipine, ryanodine, veratridine, reduced [Na]o, epinephrine, SrCl2.

Download Full-text