title: Molecular and electrophysiological evidence for "remodeling" of the L-type Ca2+ channel in persistent atrial fibrillation in humans.
abstract: Persistent atrial fibrillation (AF) is associated with shortened action potential duration (APD) and reduced atrial refractoriness. Remodeling of ion currents responsible for AP morphology has been proposed as a major mechanism in persistent AF. In the present study we investigated the activity of the cardiac L-type Ca2+ channel and the mRNA transcription of the cardiac L-type Ca2+ channel subunits in patients with persistent AF compared to patients in sinus rhythm (SR). Right atrial appendages of 10 patients in SR and of 5 patients with AF were used for myocyte isolations to record L-type Ca2+ currents (ICa,L) by the patch-clamp technique. Right atrial appendages of 16 patients in Sr and of 5 patients with AF served as sources for determining the mRNA expression of the L-type Ca2+ channel alpha 1c-, alpha 2/delta-, beta a-, and beta b/beta c-subunits by semiquantitative RT-PCR. ICa,L density was reduced by 70% (p < 0.001) in AF patients compared to the sinus rhythm group. Cell sizes, expressed as cell capacitance, were identical in both groups. mRNA expressions of the alpha 1c-subunit and the beta b/beta c-subunits were reduced in AF patients by 18.9% (p < 0.05) and 77.7% (p < 0.005), respectively, while mRNA transcriptions of the alpha 2/delta- and the beta a-subunits were not significantly different between SR and AF patients. A decrease in the availability of functional L-type Ca2+ channels in AF patients, due to reduced alpha 1c-subunit and substantial lack of beta b/beta c-subunit transcription seems to contribute to the shortening of APD and refractory periods in AF, thereby favoring increased atrial excitation rate and perpetuation of AF.
authors.affiliation: Medizinische Klinik der Universität Tübingen, Abteilung III, Germany. joachim.grammer@uni-tuebingen.de
authors.forename: J B
authors.initials: JB
authors.lastname: Grammer
authors.forename: R F
authors.initials: RF
authors.lastname: Bosch
authors.forename: V
authors.initials: V
authors.lastname: Kühlkamp
authors.forename: L
authors.initials: L
authors.lastname: Seipel
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology*; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D015220:Calcium Channels; D012333:RNA, Messenger