Search PubMed⌕ Search

Biomedical subjects

J Toyama

Publications and source records attributed to J Toyama.

At least 109 records · Page 6Linked to original sources
PubMed1992

Long-term study of recurrent vasospastic angina using coronary angiograms during ergonovine provocation tests.

Chronologic changes of coronary spasm were examined by repeated ergonovine provocation tests during angiography. A total of 322 patients who had variant angina without severe atherosclerosis demonstrated a positive response to the first test. Ninety of these patients had recurrent variant anginal symptoms after an angina-free period of 38 +/- 12 months (mean +/- SD). Of these 90 patients, 76 (84%) had symptoms or electrocardiographic (ECG) findings similar to those of the first test. The initial 9 of these 76 patients underwent a second provocation test and showed coronary responses analogous to those on the first test. Of the 90 patients, 14 (16%) had different symptoms or ECG findings from those elicited at the first episode. All 14 patients again had a positive response to a second ergonovine test and the following angiographic changes were observed in the three major vessels between the two tests. Of the 21 vessels that had spasm on the first test, eight vessels (19%) did not have spasm on the second test. Of the 21 vessels that did not demonstrate spasm on the first test, 10 (24%) demonstrated spasm on the second test. In the present study it is concluded that the majority of patients with recurrent angina seemed to have consistency in the location of coronary spasm, while in some patients the fluctuation of coronary spasm was confirmed by two ergonovine provocation tests.

Adult↗
PubMed1992

Deferoxamine, an iron chelator, reduces myocardial injury and free radical generation in isolated neonatal rabbit hearts subjected to global ischaemia-reperfusion.

The protective action of deferoxamine, an iron chelator, against functional and metabolic deteriorations of ventricular muscle, induced by ischaemia-reperfusion, was investigated in Langendorff-perfused hearts of neonatal rabbits in comparison with superoxide dismutase (SOD) plus catalase. The perfused hearts were subjected to normothermic (37 degrees C) global ischaemia for 45 min following cardiac arrest with St Thomas cardioplegic solution and then reperfused with oxygenated Krebs-Henseleit solution. In control hearts, the recovery of the left ventricular developed pressure (LVDP) after 30 min reperfusion was 50.7 +/- 3.1% (mean +/- SE, n = 5) of the pre-ischaemic value. The LVDP recovery was significantly improved in the hearts treated with deferoxamine at 10-100 microM (89.4 +/- 1.4% at 30 microM, P < 0.01 vs. control). The improvement in LVDP was less prominent when treated with 30 x 10(4) U/l SOD plus 30 x 10(4) U/l catalase (67.9 +/- 2.0%, P < 0.01 vs. deferoxamine at 30 microM). CPK leakage into the coronary effluent during the initial 5 min of reperfusion was reduced to around half of the control value with 30 microM deferoxamine (P < 0.05 vs. control), while unaffected by the addition of SOD plus catalase. Free radicals in the coronary effluent were measured with electron spin resonance spectroscopy in separate experiments by using a spin-trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). A burst of DMPO-OH signal was detected during the initial minutes of reperfusion. The intensity of DMPO-OH signal was significantly reduced by 30 microM deferoxamine to about one-third of control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of long-term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle.

1. The effects of long-term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2. ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg-1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14-0.18 micrograms ml-1 and 1.47-3.63 micrograms g-1 wet wt. respectively. 3. Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity (Vmax) was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E-4031, Cs+ and 4-aminopyridine, did not show marked reverse use-dependence. 4. APD and Vmax restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5. Acute application of amiodarone (10 microM) caused a significant decrease in APD and developed tension, as well as a marked use-dependent Vmax inhibition with fast recovery kinetics. 6. These findings suggest that a major and consistent electro-physiological effect of chronic amiodarone is repolarization delay (Class-III action) showing minimal frequency-dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class-I action would be added as an acute effect.

Action Potentials↗
PubMed1992

Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea-pig ventricular cells.

1. The effects of diprafenone and propafenone on transmembrane action potential were examined and compared in papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, both diprafenone and propafenone > or = 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. 3. In the presence of either drug, trains of stimuli at rates > or = 0.1 Hz led to an exponential decline in Vmax. A time constant (tau R) for Vmax recovery from the use-dependent block was 15.5 s for diprafenone and 8.8 s for propafenone. 4. The use-dependent block of Vmax with diprafenone was enhanced when the resting potential was depolarized by high (8, 10 mM) [K+]o, whereas that with propafenone was virtually unchanged. tau R with diprafenone was shortened by the depolarization, while that with propafenone was rather prolonged. 5. In single myocytes perfused with diprafenone or propafenone, 10 ms conditioning clamp to 0 mV caused a significant decrease in Vmax of subsequent action potential. A prolongation of the clamp pulse duration resulted in a modest enhancement of the Vmax inhibition with diprafenone, while a large enhancement of the Vmax inhibition occurred with propafenone. 6. These findings suggest that diprafenone, like propafenone, may block the sodium channel during both the activated and inactivated states. The relative contribution of inactivation block is less important for diprafenone than for propafenone. The different voltage-dependence of use-dependent block with diprafenone from propafenone would contribute to its high antiarrhythmic potency.

Action Potentials↗
PubMed1992

Protective action of iron-chelating agents (catechol, mimosine, deferoxamine, and kojic acid) against ischemia-reperfusion injury of isolated neonatal rabbit hearts.

Iron is suggested to play an important role in free radical generation during ischemia reperfusion. In the present study, the protective action of 4 iron-chelating agents, with different iron affinities, against reperfusion injury was examined in Langendorff-perfused hearts of neonatal rabbits. The chelators and their iron-binding constants (log Km) were as follows: catechol (43), mimosine (36), deferoxamine (31) and kojic acid (27). Following cardiac arrest, the hearts were subjected to global ischemia for 45 min at 37 degrees C, and then reperfused with modified Krebs-Henseleit solution for 30 min. In control, the left ventricular developed pressures (LVDP) after 30 min reperfusion recovered to 50.5 %/- 3.0% (mean +/- SEM; n = 5) of the preischemic level. In the hearts treated with catechol (30 microM), mimosine (30 microM) or deferoxamine (30 microM), the LVDP recovery was significantly improved up to 84.9 +/- 1.3, 88.2 +/- 2.9 or 87.4 +/- 1.5%, respectively (p < 0.01 vs. control). Creatine phosphokinase (CPK) leakage during the initial 5 min of reperfusion was significantly decreased to about half of control in the hearts treated with catechol, mimosine, or deferoxamine. However, the treatment with kojic acid (30 microM) showed no improvement in the LVDP recovery and CPK leakage. Free radical generation was measured with an electron spin resonance using a spin-trapping agent, 5,5-dimethyl-pyrroline-N-oxide (DMPO). The treatment with catechol, mimosine, or deferoxamine reduced the maximum intensity of DMPO-OH signal to about one third of control. However, the maximum intensity in the hearts treated with kojic acid showed a similar level to control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A model analysis for competitive binding of mexiletine and aprindine to the cardiac sodium channel.

A simulation model was developed to predict complex interaction between antiarrhythmic drugs and cardiac sodium channels. This model has four assumptions: (1) Vmax of the action potential is a linear indicator of available sodium channel conductance; (2) antiarrhythmic drugs block the channel by binding to a single common receptor site associated with the channel; (3) binding and dissociation rate constants differ for the three channel states: activated, inactivated and resting, and (4) both drug-free and drug-bound channels change states far more rapidly than binding and dissociation processes. Binding and dissociation rate constants for the three channel states were calculated from single cell experiments using guinea pig hearts. Vmax changes reflecting tonic and use-dependent sodium channel block in the presence of mexiletine and aprindine were simulated and compared with those obtained in the single cell experiments. The model predicted that 'tonic' Vmax inhibition would be enhanced, whereas 'use-dependent' ones would be attenuated after admixture of mexiletine with aprindine. The mechanisms would involve competitive interaction at the common receptor site. Single-cell experiments supported this prediction. We conclude that our simple two-drug binding model provides a useful tool to predict pharmacological interaction between class I antiarrhythmic drugs given in combination.

Action Potentials↗
PubMed1992

[Ergometric and pathologic study of a family with complex I deficiency].

We studied a family with a myopathic form of complex I deficiency with regard to the clinical symptoms, usefulness of the exercise tolerance test with an ergometer for screening of mitochondrial abnormalities, pathological findings in biopsied muscles and genetics. In this family, none of the members had disorders of the central nervous system, such as convulsions, mental deterioration or stroke-like episodes. In the two affected generations, three mothers and three children had mitochondrial abnormalities. Two children were diagnosed as having complex I deficiency. One of them, an 8-year-old girl with normal psychomotor development during infancy, began to experience easy fatigability at about 3 years of age. At the age of 5 years, she experienced respiratory distress and became unconscious. Thereafter, she had similar episodic respiratory problems with lactic acidosis. Ragged-red fibers and respiratory chain enzyme defects were detected in the biopsied muscle. Another child, a 15-year-old boy with easy fatigability but no muscle weakness, had normal respiratory chain enzyme activities and a normal oxysogram: oxygen consumption showed a normal responses when malate and pyruvate were added as substrates for the isolated mitochondria. His muscle pathology revealed rare ragged-red fibers and abnormal subsarcolemmal mitochondrial aggregation. An investigation with an ergometer showed elevated serum lactate and pyruvate levels. Only one mother had muscle weakness and hyper-lactic acidemia. The other two mothers had no muscle symptoms, but abnormal results were obtained with the ergometer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Effects of combined use of class I antiarrhythmic agents on Vmax of guinea-pig ventricular muscles.

The effects of the combined use of class-I antiarrhythmic drugs on the resting potentials (RP), amplitude of action potential (AMP), and Vmax of the action potential were investigated in guinea-pig ventricular papillary muscles that were superfused with oxygenated Krebs-Ringer solution at 35 degrees C. Disopyramide (40 microM) reduced Vmax to 68.6 +/- 3.1% (mean +/- SE, n = 5) of the control with minimal changes in RP and AMP when preparations were stimulated at 1 Hz. The addition of mexiletine (20 microM) to the solution containing disopyramide (40 microM) caused a minimal reduction of Vmax (less than 5%) for the stimulation of 1 Hz, but a significant reduction of Vmax (13% p less than 0.05) when stimulation was increased to 2 Hz. This amount of the reduction is compatible with that obtained by mexiletine alone, suggesting a simple additive Na+ channel inhibition by this drug combination. This additive effect was also observed in the recovery process of Vmax from the use-dependent block induced by train stimuli at 1 Hz. Flecainide (5 microM) reduced Vmax to 58.6 +/- 13.3% (n = 5). The addition of mexiletine to the superfusate with flecainide produced a further depression of 14 +/- 2.6% of Vmax, even at 1 Hz. This depression was larger than that produced by mexiletine, suggesting a synergistic action of the two drugs on the Na+ channel. Such information about the interaction of the class I drug combinations with the Na+ channel may be clinically important.

Action Potentials↗
PubMed1991

A combination of inactivated sodium channel blockers causes competitive interaction on dV/dtmax of single ventricular myocytes.

STUDY OBJECTIVE: The aim was to study an interaction between class I antiarrhythmic drugs on the cardiac sodium channels. DESIGN: The single pipette, whole cell clamp method was employed to control and record membrane potential. The maximum upstroke velocity (dV/dtmax) was measured as an index of sodium channel availability during treatment of the preparations with aprindine (5 microM) in combination with mexiletine (40 microM), and lignocaine (40 microM). EXPERIMENTAL MATERIAL: Single ventricular myocytes (n = 6-8 per experiment) isolated from guinea pig hearts were used. MEASUREMENTS AND MAIN RESULTS: Trains of depolarisation to 0 mV (0.2-2.0 Hz) were applied from the resting membrane potential (-85 mV) following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine or lignocaine to aprindine resulted in an increase of tonic block and a decrease of use dependent block. Because of such counteracting action, the steady state dV/dtmax during the train of depolarisation was unaffected for mexiletine, and even increased for lignocaine. Dual exponential components of dV/dtmax recovery following a 1 s conditioning depolarisation after admixture of mexiletine or lignocaine to aprindine suggest their competitive interaction on cardiac sodium channels. CONCLUSION: A combination of class I antiarrhythmic drugs having high affinity for the inactivated state of sodium channels may cause a reductive effect on dV/dtmax through competitive displacement from common receptors.

Animals↗
PubMed1991

Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats.

STUDY OBJECTIVE: The aim was to study intracellular calcium dynamics underlying positive or negative tension staircase of mammalian hearts. DESIGN: Changes in cytosolic calcium concentration [( Ca2+]i) in single ventricular myocytes were investigated using a Ca2+ indicator, fura-2. Beat to beat alterations in fura-2 fluorescence and cell edge movement on resumption of stimulation were recorded on video tape, and analysed by a computer based image processing system. EXPERIMENTAL MATERIAL: Single ventricular myocytes were enzymatically isolated from the hearts of 30 adult guinea pigs and 25 adult rats. MEASUREMENTS AND MAIN RESULTS: In guinea pig ventricular myocytes, the positive contractile staircase was associated with ascending staircases of both peak systolic and end diastolic [Ca2+]i because of a cumulative increase in diastolic [Ca2+]i. In rat ventricular myocytes, the negative contractile staircase was accompanied by a descending staircase of peak systolic [Ca2+]i, while end diastolic [Ca2+]i level was unchanged due to the rapid decay of [Ca2+]i transients. Ryanodine (10 microM) reversed the mode of [Ca2+]i and contractile staircases from negative to positive in rat myocytes, whereas it caused minimal alteration in guinea pig myocytes. CONCLUSIONS: Tension staircase of mammalian hearts depends on diastolic Ca2+ level as well as Ca2+ handling by the sarcoplasmic reticulum. The positive staircase may require progressive increase in diastolic [Ca2+]i, while the negative staircase may be mediated by depletion of activator Ca2+ in the sarcoplasmic reticulum.

Animals↗
PubMed1991

Block of cardiac sodium channels by amiodarone studied by using Vmax of action potential in single ventricular myocytes.

1. Acute effects of amiodarone on cardiac sodium channels were investigated in ventricular myocytes isolated from guinea-pig hearts, and compared with those of lignocaine. 2. Transmembrane potential was recorded and controlled by whole-cell current-clamp and voltage-clamp respectively through suction pipette electrodes. The maximum upstroke velocity (Vmax) of the action potential was used as a qualitative index of sodium channel availability. 3. In myocytes treated with amiodarone (1 microM) or lignocaine (40 microM), Vmax of reference action potential elicited at 0.03 Hz was decreased by 6-11%, indicating minimal tonic block of sodium channels. 4. Application of a single conditioning depolarization to those myocytes resulted in a significant decrease in Vmax of a subsequent test action potential. The Vmax reduction was enhanced in a single exponential function as the clamp pulse duration was prolonged. Time constants at 0 mV clamp were 25 ms for amiodarone and 122 ms for lignocaine. 5. Vmax recovery of test action potential following a 1000 ms 0 mV clamp was approximated by a dual exponential function. Time constants for the late slow component (tau R) at the resting potential level were 418 ms for amiodarone and 178 ms for lignocaine. tau R values were shortened in a voltage-dependent manner by hyperpolarization during the coupling interval. 6. These findings suggested that amiodarone, like lignocaine, blocks the sodium channel primarily when it is in the inactivated state. Both onset and offset kinetics of the block are very rapid. Such sodium channel blocking characteristics may contribute to its potent antiarrhythmic activity.

Action Potentials↗
PubMed1990

Two types of sodium channel block by class-I antiarrhythmic drugs studied by using Vmax of action potential in single ventricular myocytes.

The state-dependent sodium channel block by mexiletine, tocainide, lidocaine, OPC-88117, aprindine, quinidine, disopyramide and AN-132 was investigated in single ventricular myocytes isolated from guinea-pig hearts. A single conditioning clamp pulse with a duration from 10 ms to 1000 ms was applied from the resting potential (-82 mV) to 0 mV level using a suction pipette whole-cell voltage clamp technique, and the maximum upstroke velocity (Vmax) of a test action potential elicited 100 ms after termination of the clamp pulse was measured as an index of sodium channel availability. In myocytes treated with the eight drugs, such clamp pulse caused a significant decrease in Vmax. With mexiletine, tocainide, lidocaine, OPC-88117 and aprindine, the Vmax reduction was enhanced progressively as the clamp pulse duration was prolonged. With quinidine, disopyramide and AN-132, an appreciable Vmax reduction at the shortest clamp pulse was followed by an additional small enhancement of the Vmax decay. These findings suggest that the former group of drugs may block the sodium channel mainly during the inactivated state (inactivation blockers), whereas the latter one may do so mainly during the activated state (activation blockers). Multiple short clamp pulses caused a greater Vmax reduction than a single prolonged clamp pulse for the activation blockers, and vice-versa for the inactivation blockers. Molecular dimensions of the eight drugs, which were estimated by X-ray diffraction of crystals, did not satisfy a simple size criterion as proposed by Courtney (1988) to explain such different types of sodium channel block by Class-I drugs.

Action Potentials↗
PubMed1990

Combined application of class I antiarrhythmic drugs causes "additive", "reductive", or "synergistic" sodium channel block in cardiac muscles.

STUDY OBJECTIVE: The aim was to study the differences in cardiac sodium channel block among combinations of class I antiarrhythmic drugs. DESIGN: Conventional glass microelectrode techniques were used to record transmembrane action potentials and their maximum upstroke velocity (dV/dtmax) reflecting the sodium channel availability, during treatment of the preparations with mexiletine (20, 40 microM) in combination with aprindine (5 microM), disopyramide (40 microM), and flecainide (5 microM). EXPERIMENTAL MATERIAL: Guinea pig papillary muscles (n = 6.8 per experiment) were used for the study. MEASUREMENTS AND MAIN RESULTS: In preparations constantly stimulated at 1 Hz, a shortening of action potential duration by aprindine was further enhanced, while prolongation by disopyramide or flecainide was reduced, after additional application of mexiletine. Trains of stimuli (0.5-2.0 Hz) were applied following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine to the other three drugs resulted in an enhancement of tonic block. Use dependent block by aprindine at 0.5-1.0 Hz was reduced by 8-9% after admixture of mexiletine, reflected in net increase in dV/dtmax at steady states (reductive effect). Dual exponential components of dV/dtmax recovery from use dependent block in presence of both drugs suggest their competitive interaction on a common receptor site associated with sodium channels. Use dependent block by flecainide at 0.5-2.0 Hz was increased (p less than 0.01) after admixture of mexiletine. Steady state dV/dtmax was therefore largely inhibited by the drug combination (synergistic effect). Use dependent block in the presence of both disopyramide and mexiletine was similar to that predicted from the algebraic sum of each treatment. CONCLUSION: Combined application of class I antiarrhythmic drugs causes not only additive but also reductive or synergistic effects on dV/dtmax through modulation of use dependent block.

Action Potentials↗
PubMed1990

Electrophysiological effects of AFD-21 and AFD-19, new antiarrhythmic compounds on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of AFD-21, a newly synthesized antiarrhythmic compound, and AFD-19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, AFD-21 10(-5) M caused a slight prolongation of action potential duration (APD), while AFD-19 above 10(-6) M shortened APD in a dose-dependent manner. 3. Both AFD-21 and AFD-19 above 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. 4. In the presence of AFD-21 or AFD-19, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. A time constant for the recovery of Vmax from the use-dependent block was 2.9 s for AFD-21 and 3.6s for AFD-19. 5. The curves relating membrane potential and Vmax were shifted by AFD-21 (10(-5) M), or AFD-19 (10(-5) M) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6. In single ventricular myocytes treated with AFD-21 (10(-5) M) or AFD-19 (10(-5) M), Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that both AFD-21 and AFD-19 have use- and voltage-dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics.

Action Potentials↗
PubMed1990

ATP directly affects junctional conductance between paired ventricular myocytes isolated from guinea pig heart.

Effects of ATP on junctional conductance (gj) were investigated in paired ventricular myocytes isolated from guinea pig hearts. One cell of the pair was voltage-clamped with a single-patch pipette, and gj was measured after the perforation of the nonjunctional membrane of the partner cell. The current-voltage relation of gj was linear between -30 and +30 mV. The control gj at 5.0 mM ATP in 88 pairs of cells ranged from 100 to 1,055 nS (average, 268 nS). ATP within the range from 0.1 to 5.0 mM increased gj in a dose-dependent manner. The Hill coefficient was 2.6, and the half-maximum effective concentration of ATP was 0.68 mM. Adenylylimidodiphosphate (2 mM) caused a transient increase in gj in the presence of 0.5 mM ATP, but forskolin (30 microM), cyclic AMP (50 microM), catalytic subunit of cyclic AMP-dependent protein kinase (1 microM), and ADP (10 mM) had no significant effect on gj. The temperature coefficient of gj in the presence of 5.0 mM ATP was 1.29. These findings suggest that gj in paired ventricular myocytes is directly regulated by ATP probably through a specific ligand-receptor interaction between ATP and gap junctional channel protein.

Adenosine Diphosphate↗
PubMed1990

Mechanisms of atrial natriuretic peptide (ANP) secretion by rat hearts perfused in vitro--Ca2(+)-dependent signal transduction for ANP release by mechanical stretch.

Effects of temperature, contraction frequency, and intraatrial pressure on immunoreactive ANP release were investigated in isolated rat hearts perfused in Langendorff or working mode. A reduction of temperature from 37 C to 27 degrees C caused a decrease of ANP release by 64% indicating its marked temperature-dependency (Q10 = 2.92). An increase of atrial contraction frequency from 300 to 500/min in Langendorff-perfused hearts did not cause a significant change in the ANP release. An elevation of left atrial filling pressure of working hearts from 8 to 18 and 28 cmH2O was associated with pressure-dependent, and reversible increase of the ANP release. This pressure-induced release of ANP was inhibited in a low calcium (50% Ca2+) medium or by nifedipine (10(-7) M). N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7, 10(-7)M), a potent calmodulin inhibitor, or ryanodine (10(-8)M) had similar inhibitory action against the pressure-induced increase of ANP release. These results indicate that ANP secretion is primarily regulated by mechanical stretch or distension of the atrial wall, while the atrial contraction frequency is less important as a physiological stimulus for the secretion. The stretch-induced ANP secretion may require an influx of calcium through the voltage-dependent Ca2+ channels. It was also suggested that Ca2+ release from the sarcoplasmic reticulum leading to an activation of calcium-calmodulin kinase may be included in the intracellular processes of ANP release by mechanical stretch.

Animals↗