Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

Johannes P Hofgaard; Kathrin Banach; Sarah Mollerup; Helene Korvenius Jørgensen; Søren Peter Olesen; Niels-Henrik Holstein-Rathlou; Morten Schak Nielsen

doi:10.1007/s00424-008-0538-x

Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

Johannes P Hofgaard, Kathrin Banach, Sarah Mollerup, Helene Korvenius Jørgensen, Søren Peter Olesen, Niels-Henrik Holstein-Rathlou, Morten Schak Nielsen

15 Citations (Scopus)

Abstract

Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis that agonist-induced changes in PIP(2) can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular coupling was measured by Lucifer Yellow dye transfer in cultured neonatal rat cardiomyocytes. Conduction velocity was measured in cardiomyocytes grown on microelectrode arrays. Intercellular coupling was reduced by angiotensin II (43.7 +/- 9.3%, N = 11) and noradrenaline (58.0 +/- 10.7%, N = 11). To test if reduced intercellular coupling after agonist stimulation was caused by PIP(2)-depletion, myocytes were stimulated by angiotensin II (57.3 +/- 5.7%, N = 14) and then allowed to recover in medium with or without wortmannin (an inhibitor of PIP(2) synthesis). Intercellular coupling fully recovered in control medium (102.1 +/- 8.9%, N = 10), whereas no recovery occurred in the presence of wortmannin (69.3 +/- 7.8%, N = 12). Inhibition of PKC, calmodulin, or arachidonic acid production did not affect the response to either angiotensin II or noradrenaline. Furthermore, decreasing or increasing PIP(2) also decreased and increased intercellular coupling, respectively. This supports the role of PIP(2) in the regulation of intercellular coupling. In beating myocytes, conduction velocity was reduced by angiotensin II stimulation, and recovery after wash out was prevented by inhibition of PIP(2) production. Reductions in PIP(2) inhibit intercellular coupling in cardiomyocytes, and stimulation by physiologically relevant agonists reduces intercellular coupling by this mechanism. The reduction in intercellular coupling lowered conduction velocity.

Original language	English
Journal	Pflügers Archiv: European Journal of Physiology
Volume	457
Issue number	2
Pages (from-to)	303-13
Number of pages	10
ISSN	0031-6768
DOIs	https://doi.org/10.1007/s00424-008-0538-x
Publication status	Published - 2008

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@article{948d5f80567c11de87b8000ea68e967b,

title = "Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes",

abstract = "Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis that agonist-induced changes in PIP(2) can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular coupling was measured by Lucifer Yellow dye transfer in cultured neonatal rat cardiomyocytes. Conduction velocity was measured in cardiomyocytes grown on microelectrode arrays. Intercellular coupling was reduced by angiotensin II (43.7 +/- 9.3%, N = 11) and noradrenaline (58.0 +/- 10.7%, N = 11). To test if reduced intercellular coupling after agonist stimulation was caused by PIP(2)-depletion, myocytes were stimulated by angiotensin II (57.3 +/- 5.7%, N = 14) and then allowed to recover in medium with or without wortmannin (an inhibitor of PIP(2) synthesis). Intercellular coupling fully recovered in control medium (102.1 +/- 8.9%, N = 10), whereas no recovery occurred in the presence of wortmannin (69.3 +/- 7.8%, N = 12). Inhibition of PKC, calmodulin, or arachidonic acid production did not affect the response to either angiotensin II or noradrenaline. Furthermore, decreasing or increasing PIP(2) also decreased and increased intercellular coupling, respectively. This supports the role of PIP(2) in the regulation of intercellular coupling. In beating myocytes, conduction velocity was reduced by angiotensin II stimulation, and recovery after wash out was prevented by inhibition of PIP(2) production. Reductions in PIP(2) inhibit intercellular coupling in cardiomyocytes, and stimulation by physiologically relevant agonists reduces intercellular coupling by this mechanism. The reduction in intercellular coupling lowered conduction velocity.",

author = "Hofgaard, {Johannes P} and Kathrin Banach and Sarah Mollerup and J{\o}rgensen, {Helene Korvenius} and Olesen, {S{\o}ren Peter} and Niels-Henrik Holstein-Rathlou and Nielsen, {Morten Schak}",

note = "Keywords: Androstadienes; Angiotensin II; Animals; Animals, Newborn; Arachidonic Acid; Calcium; Cell Communication; Cells, Cultured; Dose-Response Relationship, Drug; GTP-Binding Protein alpha Subunits, Gq-G11; Gap Junctions; Myocardial Contraction; Myocytes, Cardiac; Norepinephrine; Phosphatidylinositol Phosphates; Protein Kinase C; Protein Kinase Inhibitors; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptors, Adrenergic, beta-1; Signal Transduction; Time Factors",

year = "2008",

doi = "10.1007/s00424-008-0538-x",

language = "English",

volume = "457",

pages = "303--13",

journal = "Pfl{\"u}gers Archiv: European Journal of Physiology",

issn = "0031-6768",

publisher = "Springer",

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TY - JOUR

T1 - Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

AU - Hofgaard, Johannes P

AU - Banach, Kathrin

AU - Mollerup, Sarah

AU - Jørgensen, Helene Korvenius

AU - Olesen, Søren Peter

AU - Holstein-Rathlou, Niels-Henrik

AU - Nielsen, Morten Schak

N1 - Keywords: Androstadienes; Angiotensin II; Animals; Animals, Newborn; Arachidonic Acid; Calcium; Cell Communication; Cells, Cultured; Dose-Response Relationship, Drug; GTP-Binding Protein alpha Subunits, Gq-G11; Gap Junctions; Myocardial Contraction; Myocytes, Cardiac; Norepinephrine; Phosphatidylinositol Phosphates; Protein Kinase C; Protein Kinase Inhibitors; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptors, Adrenergic, beta-1; Signal Transduction; Time Factors

PY - 2008

Y1 - 2008

N2 - Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis that agonist-induced changes in PIP(2) can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular coupling was measured by Lucifer Yellow dye transfer in cultured neonatal rat cardiomyocytes. Conduction velocity was measured in cardiomyocytes grown on microelectrode arrays. Intercellular coupling was reduced by angiotensin II (43.7 +/- 9.3%, N = 11) and noradrenaline (58.0 +/- 10.7%, N = 11). To test if reduced intercellular coupling after agonist stimulation was caused by PIP(2)-depletion, myocytes were stimulated by angiotensin II (57.3 +/- 5.7%, N = 14) and then allowed to recover in medium with or without wortmannin (an inhibitor of PIP(2) synthesis). Intercellular coupling fully recovered in control medium (102.1 +/- 8.9%, N = 10), whereas no recovery occurred in the presence of wortmannin (69.3 +/- 7.8%, N = 12). Inhibition of PKC, calmodulin, or arachidonic acid production did not affect the response to either angiotensin II or noradrenaline. Furthermore, decreasing or increasing PIP(2) also decreased and increased intercellular coupling, respectively. This supports the role of PIP(2) in the regulation of intercellular coupling. In beating myocytes, conduction velocity was reduced by angiotensin II stimulation, and recovery after wash out was prevented by inhibition of PIP(2) production. Reductions in PIP(2) inhibit intercellular coupling in cardiomyocytes, and stimulation by physiologically relevant agonists reduces intercellular coupling by this mechanism. The reduction in intercellular coupling lowered conduction velocity.

AB - Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis that agonist-induced changes in PIP(2) can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular coupling was measured by Lucifer Yellow dye transfer in cultured neonatal rat cardiomyocytes. Conduction velocity was measured in cardiomyocytes grown on microelectrode arrays. Intercellular coupling was reduced by angiotensin II (43.7 +/- 9.3%, N = 11) and noradrenaline (58.0 +/- 10.7%, N = 11). To test if reduced intercellular coupling after agonist stimulation was caused by PIP(2)-depletion, myocytes were stimulated by angiotensin II (57.3 +/- 5.7%, N = 14) and then allowed to recover in medium with or without wortmannin (an inhibitor of PIP(2) synthesis). Intercellular coupling fully recovered in control medium (102.1 +/- 8.9%, N = 10), whereas no recovery occurred in the presence of wortmannin (69.3 +/- 7.8%, N = 12). Inhibition of PKC, calmodulin, or arachidonic acid production did not affect the response to either angiotensin II or noradrenaline. Furthermore, decreasing or increasing PIP(2) also decreased and increased intercellular coupling, respectively. This supports the role of PIP(2) in the regulation of intercellular coupling. In beating myocytes, conduction velocity was reduced by angiotensin II stimulation, and recovery after wash out was prevented by inhibition of PIP(2) production. Reductions in PIP(2) inhibit intercellular coupling in cardiomyocytes, and stimulation by physiologically relevant agonists reduces intercellular coupling by this mechanism. The reduction in intercellular coupling lowered conduction velocity.

U2 - 10.1007/s00424-008-0538-x

DO - 10.1007/s00424-008-0538-x

M3 - Journal article

C2 - 18536930

SN - 0031-6768

VL - 457

SP - 303

EP - 313

JO - Pflügers Archiv: European Journal of Physiology

JF - Pflügers Archiv: European Journal of Physiology

IS - 2

ER -

Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

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