ISSN:
1432-2013
Keywords:
Sodium current
;
Na-Ca exchange
;
Excitation-contraction coupling
;
Cardiac myocyte
;
Calcium transient
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract We investigated the role of the fast sodium current (I Na) in triggering Ca release from the sarcoplasmic reticulum (SR), using adult rat left ventricular myocytes, loaded with Fura-2 to measure intracellular Ca (Cai), which were whole-cell patch-clamped at 35–37°C. Before each test pulse, a series of 400-ms conditioning pulses to +10 mV were applied to establish a constant level of SR Ca load. Pulses were applied every 15 s. A test pulse from −80 mV to −50 mV elicited a rapidI Na and a phasic Cai transient. When the solution perfusing a myocyte was rapidly switched for 15 s before a test pulse to one containing the L-type Ca channel blocker nifedipine (20 μM), the test pulse still activatedI Na and a phasic Cai transient, the amplitude of which was not significantly different from control (P〉0.05;t-test). When a rapid switch to 20 μM nifedipine plus 30 μM tetrodotoxin (TTX) was made 15 s before a test pulse, bothI Na and the Cai transient were completely abolished (n=6). When a switch was made to Na-free (Li) solution, which contained 20 μM nifedipine to block L-type Ca current,I Ca,L, there was no significant difference in the Cai transient amplitude from that of control (P〉0.05;n=6). Brief depolarising test pulses (−80 mV to +20 mV, 10 ms duration) to simulate membrane potential escape also elicited a Cai transient which attained 90.0% (±2.8%;n=7) of the Cai transient activated by a conditioning pulse to +10 mV. The Cai transient with a brief pulse was not significantly affected by application of 20 μM nifedipine (P〉0.05), but adding TTX with nifedipine reduced the Cai transient amplitude to 76.9% (±6.8%;P〈0.02;n=8). In four cells, the Cai transient remaining in the presence of nifedipine plus TTX was abolished by adding 5 mM Ni. These data are consistent with “voltage escape” during activation ofI Na leading to a trigger Ca entry via a mechanism other than L-type Ca channels or subsarcolemmal Na accumulation with reverse Na-Ca exchange. The block by Ni of the Cai transient suggests that a brief membrane potential escape might directly activate reverse mode Na-Ca exchange to trigger SR release, and this mechanism would seem to account largely for the Cai transient which accompaniesI Na in rat myocytes, under these experimental recording conditions.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01837401
