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Am J Physiol Heart Circ Physiol 273: H2481-H2489, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 5, H2481-H2489, November 1997

Ionic basis of ryanodine's negative chronotropic effect on pacemaker cells isolated from the sinoatrial node

Jin Li, Jihong Qu, and Richard D. Nathan

Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430

Spontaneous electrical activity and indo 1 fluorescence ratios were recorded simultaneously in cultured pacemaker cells isolated from the rabbit sinoatrial node. Ryanodine (10 µM) reduced the amplitude of action potential-induced intracellular Ca2+ (Ca2+i) transients by 19 ± 3%, increased the time constant for their decay by 51 ± 5%, and slowed spontaneous firing by 32 ± 3%. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester (AM; 25 µM) inhibited the Ca2+i transients and slowed spontaneous firing by 28 ± 4%. Ryanodine did not alter hyperpolarization-activated or time-independent inward current, but it reduced the sum of L- and T-type Ca2+ currents (ICa,L and ICa,T) in both the presence and absence of BAPTA-AM. In contrast, ICa,L was unchanged by ryanodine. Slow inward current tails, presumed to be Na/Ca exchange current (INa/Ca), were abolished by BAPTA or ryanodine. The results suggest that a decrement of ICa,T, due to reduction of the intracellular Ca2+ concentration or a direct effect of ryanodine on T-type Ca2+ channels, contributes to the negative chronotropic effect. Another possibility, based primarily on theory and results in other preparations, is that a reduction of INa/Ca, as a consequence of the smaller action potential-induced Ca2+i transients, contributes to the effect of ryanodine.

L-type calcium current; T-type calcium current; sodium/calcium exchange current; indo 1; 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid; perforated-patch voltage-clamp technique


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