@entity955 ( @entity955 ) is a @entity943 which affects millions of @entity1 in Europe alone. This @entity943 is associated with increased morbidity and mortality and it gets increasingly difficult to treat when allowed to persist for longer periods. Pharmacologically, @entity955 therapy is limited by suboptimal efficacy and the risk of both cardiac and extracardiac side effects. Current antiarrhythmic drugs work by inhibiting several ionic currents in the heart, while new drug development pursues atrial-selectivity by targeting ion currents predominantly present in the atria, with the purpose of reducing the risk of ventricular proarrhythmic effects and other @entity137 . Among such targets are the ion channels conducting the @entity934 activated @entity972 current (IK,ACh) and the ultra-rapid delayed rectifier @entity972 current (IKur). During the last decade, another possible atrial specific target has gained attention, which is the small conductance @entity141 activated K+ (SK) channel that conducts the IKCa current. Recently, our group and others have documented IKCa inhibition to be antiarrhythmic in a number of in vivo and ex vivo animal models both in restoring sinus rhythm and in preventing @entity955 induction, however the exact antiarrhythmic mechanisms have not been elucidated. SK channels have furthermore been reported to be involved in electrical remodeling in @entity1 suffering from @entity955 and @entity712 , while their exact function in these diseases remains unknown. In this thesis the aim was to explore the antiarrhythmic mechanisms generated by IKCa inhibition and to study whether SK channels and IKCa is functionally present in @entity1 atrial and ventricular tissue. The results presented in this thesis, confirm the antiarrhythmic effects of several SK channel inhibitors and show the presence of selective IKCa current in @entity121 and isolated cardiomyocytes from cardiac @entity1 , while ventricular IKCa current was not detected. In atrial tissue from @entity1 in chronic @entity955 SK channels along with the detectable IKCa current were downregulated.     In conclusion, the present thesis and the three published papers report evidence for the existence of functional SK channels and IKCa predominantly present in @entity1 atria and provide elucidation of the possible antiarrhythmic mechanisms of IKCa inhibition.

Antiarrhythmic principle of SK channel inhibition in XXXX .

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'people'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity955 :: ('MESH:D001281', 'Disease') :: ['Atrial fibrillation', 'AF'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity943 :: ('MESH:D001145', 'Disease') :: ['cardiac arrhythmia', 'arrhythmia'] @entity121 :: ('MESH:D009135', 'Disease') :: ['atrial muscle preparations'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity955 :: (MESH:D001281,Disease) :: ['atrial fibrillation']
