L-type calcium channel activity in human atrial myocytes as influenced by 5-HT.
5-Hydroxytryptamine (10 mumol/l; 5-HT) exerted a positive inotropic effect associated with an increase in the Ca2+ current (ICa) in the human right atrium. For detailed analysis, L-type Ca2+ channel currents were recorded from cell-attached patches using 100 mmol/l Ba2+ as charge carrier. Ca2+ channel activity was identified, first, by burst-like inwardly directed currents and, second, by the appearance of long channel openings promoted by Bay K 8644 (1 mumol/l) upon repetitive depolarizations from -80 to 0 mV. The unitary conductance of the Ca2+ channel amounted to 25.8 pS. During superfusion with 5-HT, ensemble averaged (mean) current was enhanced by about 60%. The increase in mean current was brought about by an increase in the channel availability, defined as the ratio of sweeps containing Ca2+ channel activity to the total number of depolarizations. The open probability of a single Ca2+ channel within a sweep with channel activity, unitary conductance, mean open and mean shut times of the channel, however, remained unaffected during superfusion with 5-HT (n = 10). The 5-HT-induced increase in macroscopic ICa in the human atrium can therefore be explained by an enhanced availability of Ca2+ channels to open upon depolarization. The observed changes in gating properties of the human Ca2+ channel by 5-HT are very similar to those which are known from isoprenaline-induced cAMP-dependent phosphorylation of the Ca2+ channel protein in other tissues.
Jahnel
U
U
Pharmakologisches Institut, Universität Mainz, Germany.
Nawrath
H
H
Rupp
J
J
Ochi
R
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002675:Child, Preschool; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D015640:Ion Channel Gating / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D012701:Serotonin / Q000494:pharmacology*
D015220:Calcium Channels; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000242:Cyclic AMP; D007545:Isoproterenol