Mice display sex differences in halothane-induced polymorphic ventricular tachycardia.
BACKGROUND
Molecularly engineered mice are extensively used as models of cardiovascular diseases, yet little is known about sex differences in the electrophysiology of mouse hearts.


RESULTS
This study investigated the influence of sex on drug-induced polymorphic ventricular tachycardia (PVT) in Langendorff-perfused male and female mice hearts (n=54) by injecting a bolus of halothane (1.75 mmol/L) in the perfusate while recording ECGs or optical action potentials (APs). There were no statistically significant differences between male and female hearts (n=54) with respect to mean RR (193+/-5 ms), PR (47+/-1 ms), QT intervals (101+/-3 ms), optical AP durations (APD(75)=23.11+/-4.2 ms), dispersion of refractory periods, and conduction velocities (n=5 male and 5 female). Halothane induced PVTs lasting a mean duration of 90 seconds; in female hearts, 55% of PVTs lasted longer than the median, whereas in male hearts 17% exceeded the mean (P<0.05). The total duration of PVTs exposed a marked sex difference, 378+/-144 seconds in female versus 27+/-10 seconds in male hearts (P<0.05). In optically mapped male hearts, halothane reduced APD(75) (17.61+/-1.6 ms) and then elicited VTs (n=6 of 6), but in female hearts, halothane elicited PVTs (n=1 of 6) or arrested the hearts (n=5 of 6). Except for KCNE1, Northern blots (KCNQ1, MERG, Kv1.5, connexins 40 and 43, TREK1, and TASK1) did not detect sex differences.


CONCLUSIONS
This mouse model reveals sex difference in response to a pharmacological challenge yet does not display sex differences in standard electrophysiological parameters. Differences in KCNE1 may contribute to sex differences uncovered by halothane.
Drici
Milou-Daniel
MD
Centre National de la Recherche Scientifique-Unité Mixte de Recherche, Sophia Antipolis, 06560 Valbonne, France.
Baker
Linda
L
Plan
Patricia
P
Barhanin
Jacques
J
Romey
Georges
G
Salama
Guy
G
D000200:Action Potentials; D000818:Animals; D018780:Body Surface Potential Mapping; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006221:Halothane; D006321:Heart / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000096:biosynthesis; D012032:Refractory Period, Electrophysiological; D012737:Sex Factors; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology
D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; C059983:potassium channel protein I(sk); D006221:Halothane