MOLECULAR AND FUNCTIONAL PROPERTIES OF T-TYPE CA~(2+) CHANNEL IN MOUSE EMBRYONIC HEARTS

摘要

[Aim] T-type Ca~(2+) channels are implicated in cardiac cell growth and in pacemaker activities. We analyzed the subtype expression of T-type channel during development in mouse hearts. [Method] Ca~(2+) currents were recorded in ventricular myocytes from mice of E9.5, El 8 and 10 week-old (adult) by a patch clamp method. Subtype expression of T-type channel genes (Ca_v3.1 and Ca_v3.2) was quantified by a real time PCR. [Result] T-type current (I_(Ca-T)) was detected at E9.5 and at E18 with similar current densities, while I_(Ca-T) was not detected at adulthood. There were no differences in voltage dependence of activation and inactivation, and time dependency of recovery from inactivation between I_(Ca-T) at E9.5 and that at E18. Low dose of Ni~+ (30 muM) blocked I_(Ca-T) both at E9.5 (IC50 = 31u,M) and at E18 (IC_(50) = 26 muM) and the inhibition was comparable to those described for cloned Ca_v3.2 channels. Expression of Ca_v3.2 mRNA was abundant at E9.5, but decreased in steps from E18 to adulthood. In contrast, Ca_v3.1 mRNA was substantially expressed both at E18 and at adulthood but below the level of detection at E9.5. [Conclusion] The dominant subtype of T-type channel in mouse hearts at early to late embryonic period is Ca_v3.2.