Prenatal exposure to carbon monoxide affects postnatal cellular electrophysiologic remodeling of the rat heart.

During postnatal development, ventricular myocytes (VM) undergo an increase in transient otward current (Ito) density, responsible for the reduction of the action potential duration (APD), and a decrease of the pacemaker current (If) expression, likely associated with the disappearance of spontaneous activity. Prenatal exposure to a concentration of carbon monoxide (CO) has been shown to produce several developmental alterations, including changes in the electrical properties of rat skeletal muscle fibers. We studied postnatal electrophysiological changes in VM isolated from rats of different ages (1 to 5, 8 to 15, 20 to 30 days) exposed to 0 (CTR) or 150 ppm CO during in utero life. Patch-clamped VM were superfused with a normal Tyrode's solution (to measure action potential) or appropriately modified Tyrode's solutions (to measure Ito and If). Postnatal increase in membrane capacitance, an index of cell size, was similar in both groups (from 14±1 to 60±5 pF in CTR; from 15±1 to 59±5 pF in CO). While all measured values were not different in the two groups early after birth, differences were observed during growth. APD progressively decreased in CTR (from 131±24 ms at 5 days to 76±13 ms at 28 days) but not in CO rats, (157±28 ms at 28 days, p<0.05 vs CTR). Similarly, Ito density, which significantly increased in CTR from 4.1±0.7 pA/pF to 11.8±3.4 pA/pF (p<0.01), remained low in CO rats (5.8±0.9 pA/pF at 28 days, p<0.01 vs CTR). If density decreased by 75% from 1 to 28 days in CTR, but remained high in CO rats (at 28 days: 2.7 pS/pF vs 0.7 pS/pF in age-matched CTR, p<0.05). In conclusion, exposure to CO during the fetal life affect the normal process of electrophysiological maturation of the cardiac ventricular myocyte.