Inhibition and Rapid Recovery of Ca <sup>2+</sup> Current During Ca <sup>2+</sup> Release From Sarcoplasmic Reticulum in Guinea Pig Ventricular Myocytes

Circulation Research - Tập 76 Số 1 - Trang 102-109 - 1995
Karin R. Sipido1, Geert Callewaert1, Edward Carmeliet1
1From the Laboratory of Physiology, University of Leuven (Belgium).

Tóm tắt

Abstract We have investigated the modulation of the L-type Ca 2+ channel by Ca 2+ released from the sarcoplasmic reticulum (SR) in single guinea pig ventricular myocytes under whole-cell voltage clamp. [Ca 2+ ] i was monitored by fura 2. By use of impermeant monovalent cations in intracellular and extracellular solutions, the current through Na + channels, K + channels, nonspecific cation channels, and the Na + -Ca 2+ exchanger was effectively blocked. By altering the amount of Ca 2+ loading of the SR, the time course of the Ca 2+ current (I Ca ) could be studied during various amplitudes of Ca 2+ release. In the presence of a large Ca 2+ release, fast inhibition of I Ca occurred, whereas on relaxation of [Ca 2+ ] i , fast recovery was observed. The time course of this transient inhibition of I Ca reflected the time course of [Ca 2+ ] i . However, the inhibition seen in the first 50 ms, ie, the time of net Ca 2+ release from the SR, exceeded the inhibition observed later during the pulse, suggesting the existence of a higher [Ca 2+ ] near the channel during this time. Transient inhibition of I Ca during Ca 2+ release was observed to a similar degree at all potentials. It could still be observed in the presence of intracellular ATP-γ-S and of cAMP. Therefore, we conclude that the modulation of I Ca by Ca 2+ release from the SR is not related to dephosphorylation. It could be related to a reduction in the driving force and to a direct inhibition of the channel by [Ca 2+ ] i . The observation that the degree of inhibition does not depend on membrane potential suggests that the Ca 2+ binding site for this modulation is located outside the pore. The transient nature of the modulation of I Ca by Ca 2+ release will contribute to the recovery of I Ca during prolonged action potentials.

Từ khóa


Tài liệu tham khảo

10.1007/BFb0031019

10.1113/jphysiol.1991.sp018528

10.1113/jphysiol.1994.sp020037

10.1083/jcb.107.6.2587

10.1161/res.68.3.1660357

10.1161/res.56.1.2578335

10.1113/jphysiol.1988.sp017372

10.1007/BF00581904

10.1126/science.2176745

10.1016/0896-6273(92)90159-B

Imredy JP, Yue DT. Ca-sensitive inactivation of L-type Ca channels: key role of an enduring closed state outside the normal activation pathway. Biophys J. 1993;64:A204. Abstract.

10.1007/BF00370266

10.1113/jphysiol.1991.sp018876

10.1113/jphysiol.1982.sp014321

10.1038/341065a0

10.1113/jphysiol.1993.sp019724

Hirano Y, Hiraoka M. Ca2+-dependent potentiation and inactivation of single cardiac L-type calcium channel currents under optical monitoring of intracellular calcium concentration. Biophys J. 1993;64:A203. Abstract.

10.1073/pnas.84.11.3941

10.1113/jphysiol.1988.sp017341

10.1113/jphysiol.1988.sp017342

Hryshko LV, Bers DM. Ca current facilitation during post-rest recovery depends on Ca entry. Am J Physiol. 1990;259:H951-H961.

10.1161/res.63.2.2456166

Mitra R, Morad M. A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates. Am J Physiol. 1985;249:H1056-H1060.

10.1007/BF00656997

10.1016/S0021-9258(19)83641-4

10.1113/jphysiol.1988.sp017331

10.1152/ajpcell.1989.257.1.C147

Bers DM. Excitation-Contraction Coupling and Cardiac Contractile Force. Norwell Mass: Kluwer Academic Publishers; 1991:71-108.

10.1113/jphysiol.1992.sp019246

10.1126/science.2158146

10.1113/jphysiol.1990.sp018233

10.1113/expphysiol.1992.sp003624

10.1073/pnas.89.10.4417

10.1161/res.68.2.1991347

10.1085/jgp.99.3.391

10.1113/jphysiol.1993.sp019793

Yount RG. ATP analogs. Adv Enzymol Relat Areas Mol Biol. 1975;43:1-56.

10.1111/j.1432-1033.1987.tb11436.x

Hille B. Ionic Channels of Excitable Membranes. 2nd ed. Sunderland Mass: Sinauer Associates Inc; 1992:395-397.

10.1016/0143-4160(92)90046-U

10.1093/cvr/26.10.923

10.1016/0005-2736(91)90239-5

10.1016/0014-5793(90)81467-3

10.1113/jphysiol.1992.sp019028

10.1113/jphysiol.1992.sp019153

10.1016/S0006-3495(88)83178-3

10.1085/jgp.97.2.271

10.1016/S0006-3495(92)81615-6

10.1016/S0006-3495(87)83192-2

10.1093/cvr/26.5.433

10.1172/JCI112701

10.1161/res.64.5.2468430

10.1161/res.70.3.1371428

Thông tin
Thông tin xuất bản

Circulation Research

Tập 76 Số 1

102-109

Thông tin tác giả