Zhang, Z Xu, YF Song, HT Rodriguez, J Tuteja, D Namkung, Y Shin, HS Chiamvimonvat, N 2024-01-21T10:37:51Z 2024-01-21T10:37:51Z 2021-09-01 2002-05-17 0009-7330 https://pubs.kist.re.kr/handle/201004/139522 We directly examined the role of the Ca(v)1.3 (alpha(1D)) Ca2+ channel in the sinoatrial (SA) node by using Ca(v)1.3 Ca2+ channel-deficient mice. A previous report has shown that the null mutant (Ca(v)1.3(-/-)) mice have sinus bradycardia with a prolonged PR interval. In the present study, we show that spontaneous action potentials recorded from the SA nodes show a significant decrease in the beating frequency and rate of diastolic depolarization in Ca(v)1.3(-/-) mice compared with their heterozygous (Ca(v)1.3(+/-)) or wild-type (WT, Ca(v)1.3(+/+)) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca2+ currents (I(CaL)s) recorded in single isolated SA node cells from Ca(v)1.3(-/-) mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Ca(v)1.2 (alpha(IC)) versus Ca(v)1.3 Ca2+ channel subunits was directly compared by using a heterologous expression system without 0 coexpression. Similar to the I-Ca.L recorded in the SA node of Ca(v)1.3(-/-) mutant mice, the Ca(v)1.2 Ca2+ channel shows a depolarization shift in the voltage-dependent activation compared with that in the Ca(v)1.3 Ca2+ channel. In summary, using gene-targeted deletion of the Ca(v)1.3 Ca2+ channel, we were able to establish a role for Ca(v)1.3 Ca2+ channels in the generation of the spontaneous action potential in SA node cells. English LIPPINCOTT WILLIAMS & WILKINS BULLFROG SYMPATHETIC NEURONS PANCREATIC BETA-CELLS HEART-RATE REGULATION CA2+ CHANNELS PACEMAKER ACTIVITY IONIC CURRENT CALMODULIN SUBUNIT INACTIVATION CLAMP Functional roles of Ca(v)1.3 (alpha(1D)) calcium channel in sinoatrial nodes - Insight gained using gene-targeted null mutant mice Article 10.1161/01.RES.0000018003.14304.E2 1 CIRCULATION RESEARCH, v.90, no.9, pp.981 - 987 CIRCULATION RESEARCH 90 9 981 987 scie scopus 000175761900008 Cardiac & Cardiovascular Systems Hematology Peripheral Vascular Disease Cardiovascular System & Cardiology Hematology Article BULLFROG SYMPATHETIC NEURONS PANCREATIC BETA-CELLS HEART-RATE REGULATION CA2+ CHANNELS PACEMAKER ACTIVITY IONIC CURRENT CALMODULIN SUBUNIT INACTIVATION CLAMP sinoatrial nodes Ca(v)1.3 (alpha(1D)) calcium channels