Molecular and electrophysiological evidence for "remodeling" of the L-typeCa2+ channel in persistent atrial fibrillation in humans

Persistent atrial fibrillation (AF) is associated with shortened action pot ential duration (APD) and reduced atrial refractoriness. Remodeling of ion currents responsible for AP morphology has been proposed as a major mechani sm in persistent AF. In the present study we investigated the activity of t he cardiac L-type Ca2+ channel and the mRNA transcription of the cardiac L- type Ca2+ channel subunits in patients with persistent AF compared to patie nts 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 (I-Ca,I-L) by the patch-clamp technique. Right atrial appendages of 16 patients in SR and of 5 patients with AF served as sources for deter mining 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. I-Ca,I-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 id entical in both groups. mRNA expressions of the alpha(1c)-subunit and the b eta(b)/beta(c)-subunits were reduced in AF patients by 18.9 % (p < 0.05) an d 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 Ca 2+ channels in AF patients, due to reduced alpha(1c)-subunit and substantia l 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.