Inactivation of the calcium current is involved in overdrive suppression of rabbit sinoatrial node cells.
The contribution of inactivation of the L-type Ca2+ current (iCa) to overdrive suppression was investigated in rabbit sinoatrial (SA) node cells by use of the whole cell patch-clamp technique. In the current-clamp mode, rapid stimulation (6.7 Hz) for 30 s was followed by a transient increase in the cycle length of spontaneous action potentials of 135 +/- 52% (n = 3), i.e., "overdrive suppression." The iCa was measured in the voltage-clamp mode in the presence of 30 microM tetrodotoxin. An increase in the rate of depolarizing pulses (to 0 mV for 100 ms) from 1 to 6.7 Hz from a holding potential (HP) of -40 mV resulted in an abrupt, followed by a progressive, decrease in iCa; after 30 s of stimulation at 6.7 Hz, iCa was reduced to 15.5 +/- 1.8% (n = 4) of the control at 1 Hz. With an HP of -80 mV, a similar increase in the pulse rate caused much less reduction in iCa. When spontaneous action potentials were interrupted by a 30-s train of high-frequency voltage-clamp pulses (to 0 mV for 100 ms; 6.7 Hz) from an HP of -40 mV, there was again a marked decrease in iCa during the train, and after the train there was a transient suppression of spontaneous activity. In contrast, a similar interruption by high-frequency voltage-clamp pulses from an HP of -80 mV caused no decrease in iCa, and there was no suppression of spontaneous activity after the train. Neither delayed rectifier K+ current nor hyperpolarization-activated current was affected after a train of high-frequency voltage-clamp pulses. These findings suggest that overdrive suppression in the SA node is, in part at least, the result of a rate- and voltage-dependent inactivation of iCa.
Watanabe
E I
EI
Department of Circulation, Nagoya University, Japan.
Honjo
H
H
Boyett
M R
MR
Kodama
I
I
Toyama
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D004553:Electric Conductivity; D004558:Electric Stimulation; D005260:Female; D008297:Male; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D002118:Calcium