Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation

@article{Weng2002PharmacologicalMO,
  title={Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation},
  author={Stephan Weng and Melani Lauven and Thomas Schaefer and Lioudmila Polontchouk and Rajiv Grover and Stefan Dhein},
  journal={The FASEB Journal},
  year={2002},
  volume={16}
}
Antiarrhythmic peptides enhance gap junction current in pairs of cardiomyocytes and coupling in cardiac tissue. To elucidate the underlying mechanisms, we investigated the effects of the antiarrhythmic peptide AAP10 (GAG‐4Hyp‐PY‐CONH2) on pairs of adult guinea pig ventricular cardiomyocytes and pairs of HeLa cells transfected with rat cardiac connexin 43 (Cx43). By using a double‐cell voltage‐clamp technique in pairs of cardiomyocytes, we found that under control conditions the gap junction… 
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Human cardiac gap-junction coupling: effects of antiarrhythmic peptide AAP10.
TLDR
The antiarrhythmic peptide AAP10, which improves gap-junctional intercellular coupling and prevents uncoupling by acidification in human cardiomyocytes, might be useful for antiarrHythmic strategies regarding arrhythmias caused by uncouplings of Cx43 and Cx45, but not Cx40.
Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides
TLDR
Antiarrhythmic peptides are effective against ventricular tachyarrhythmias, such as late ischaemic ventricular fibrillation, CaCl2 or aconitine-induced arrhythmia, and it is still a matter of debate whether these drugs also act against atrialfibrillation.
Desipramine prevents cardiac gap junction uncoupling
TLDR
In isolated hearts, ischemia resulted in significantly increased dispersion of activation–recovery intervals, loss of membrane Cx43, and dephosphorylation of CX43, which all could be prevented by desipramine.
Pharmacological modulation of connexin‐formed channels in cardiac pathophysiology
TLDR
This review focuses on compounds that increase gap junctional communication, thereby increasing the conduction velocity and decreasing the risk of arrhythmias, and the Cx mimetic peptides Gap 26 and Gap 27 are pharmalogical agents with a favorable clinical safety profile.
Pharmacological modulation and differential regulation of the cardiac gap junction proteins connexin 43 and connexin 40
A new role for extracellular Ca2+ in gap-junction remodeling: studies in humans and rats
TLDR
It is concluded that extracellular calcium (24 h exposure) seems to up-regulate Cx40 but not Cx43, while cyclosporin A completely abolished the Ca2+-induced changes, while verapamil was ineffective.
Enhancement of ventricular gap-junction coupling by rotigaptide.
TLDR
It is demonstrated that therapeutic concentrations of rotigaptide increase the resting gap-junction conductance and reduce the magnitude and kinetics of steady-state inactivation in a concentration-dependent manner.
Subchronic alpha‐ and beta‐adrenergic regulation of cardiac gap junction protein expression
  • A. Salameh, C. Frenzel, +7 authors S. Dhein
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2006
TLDR
Adrenergic stimulation of cardiomyocytes can enhance Cx43 expression thereby increasing cellular coupling, indicating a possible role for catecholamines in the regulation of cardiac gap junction expression in cardiac disease.
Antiarrhythmic peptide AAP10 prevents arrhythmias induced by protein kinase C activation in rabbit left ventricular wedges.
TLDR
AAP10 can prevent PMA-induced rabbit ventricular arrhythmias by attenuating the increase of Tp-e and the decrease of expression of Cx43, and these data suggest that increasing gap junction coupling prevents arrh rhythmias induced by protein kinase C activation.
The anti-arrhythmic peptide AAP10 remodels Cx43 and Cx40 expression and function
TLDR
It is proposed that AAP10 is a versatile peptide that remodels metabolic coupling via Cx43 and to a lesser extent Cx40 gap junction channels via an initial protein-kinase-C-dependent pathway modifying local responses at the plasma membrane.
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