It is well known that women have a higher resting heart rate than men, but the rate-corrected QT interval of the electrocardiogram is significantly longer in women than in men (Bazett, 1920). The basis for this sex difference is unclear, but is likely to reflect the influence of the sex hormones on ventricular repolarisation. Previous reports using the rabbit suggest a key role for testosterone in somehow shortening ventricular repolarisation (Pham & Rosen, 2002). On the other hand, the influence of oestrogen and progesterone remains unclear, partly due to the abbreviated nature of the oestrus cycle in female rabbits. We have therefore recently suggested that the guinea-pig, which has an oestrus cycle similar to the human, may be useful for the investigation of the influence of the sex hormones on ventricular repolarisation (James & Hancox, 2003). However, at present there is no information available concerning the existence of sex differences in ventricular repolarisation in the guinea-pig. The objective of this study was to investigate sex-related differences in ion currents and action potentials recorded from isolated guinea-pig ventricular myocytes.

Male and female guinea-pigs were humanely killed and ventricular myocytes isolated by enzymatic and mechanical dispersion. Oestrus cycles of females were monitored by examination of the vulva and the vaginal membrane and ventricular myocytes isolated on the day of oestrus (day 0) and 4 days post-oestrus (day 4). Myocytes were superfused with a standard Tyrode solution (pH 7.35, 35 °C) and ion currents and action potentials recorded by whole-cell patch-clamp using a K⁺-rich pipette solution containing EGTA. Currents were normalised for cell size. Data are expressed as means ± S.E.M. and statistical comparisons made by one-way ANOVA with Student-Newman-Keuls post-hoc test. P < 0.05 was accepted as significant.

The L-type Ca²⁺ current (I_Ca) measured as the peak inward current on depolarisation to +10 mV (holding potential = -40 mV) was significantly larger in male myocytes (-7.41 ± 0.8 pA pF^-1, n = 12) than in day 0 (-5.5 ± 0.5 pA pF^-1, n = 11) and day 4 (-4.1 ± 0.3 pA pF^-1, n = 10) female myocytes. Moreover, I_Ca differed significantly between day 0 and day 4 female myocytes, strongly suggesting that I_Ca density varies around the oestrus cycle. The density of inward rectifier K⁺ current (I_K1) measured at -120 mV was also significantly greater in male myocytes than in female myocytes either at day 0 or day 4. Delayed rectifier (I_K) tail currents measured following pulses to +20 mV were significantly different between male and female day 4 myocytes, but not between male and female day 0 myocytes. Action potential duration at 90 % repolarisation (APD₉₀) was significantly shorter in male myocytes than in female myocytes at day 0, but not at day 4, consistent with the combined differences in I_K and I_Ca between the three groups.

Taken together, these findings demonstrate that there are sex-related differences in ventricular repolarisation in guinea-pig ventricular myocytes.