期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：4
页码：1051-1056
DOI：10.1073/pnas.0305167101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The hyperpolarization-activated cation channels (Ih) play a distinct role in rhythmic activities in a variety of tissues, including neurons and cardiac cells. In the present study, we investigated whether Ca2+ can permeate through the hyperpolarization-activated pacemaker channels (HCN) expressed in HEK293 cells and Ih channels in dorsal root ganglion (DRG) neurons. Using combined measurements of whole-cell currents and fura-2 Ca2+ imaging, we found that there is a Ca2+ influx in proportion to Ih induced by hyperpolarization in HEK293 cells. The Ih channel blockers Cs+ and ZD7288 inhibit both HCN current and Ca2+ influx. Measurements of the fractional Ca2+ current showed that it constitutes 0.60 {+/-} 0.02% of the net inward current through HCN4 at -120 mV. This fractional current is similar to that of the low Ca2+-permeable AMPA-R ({alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) channels in Purkinje neurons. In DRG neurons, activation of Ih for 30 s also resulted in a Ca2+ influx and an elevated action potential-induced secretion, as assayed by the increase in membrane capacitance. These results suggest a functional significance for Ih channels in modulating neuronal secretion by permitting Ca2+ influx at negative membrane potentials.
