Properties of veratridine-modified single Na+ channels in guinea pig ventricular myocytes.
Modification of single Na+ channels by the alkaloid neurotoxin veratridine was investigated in guinea pig ventricular myocytes using the cell-attached configuration of the patch-clamp technique. Pipette application of veratridine (50 microM) induced long-lasting openings with two different single-channel conductances of 7.6 and 3.0 pS, in addition to normal type of short openings with a single-channel conductance of 16 pS. The veratridine-modified high- and low-conductance channels appeared commonly, and they could coexist with the normal one in the same patch. The open-time distributions for the high- and low-conductance channels could be fitted by a single exponential. The mean open time for the high- and low-conductance events ranged between 19.1 ms at -120 mV and 86.0 ms at -10 mV and between 4.5 ms at -120 mV and 16.2 ms at -10 mV, respectively. The closed-time distributions for the two conductance channels consisted of at least two components, and their values and voltage dependence were similar. External Ca2+ block resulted in an apparent reduction of unitary current amplitudes with a similar voltage dependence and affinity for Ca2+ in the high- and low-conductance channels. However, the low-conductance channel was more resistant to tetrodotoxin than the high one. The probability of simultaneous occurrence of the high and low events was equal to the product of the probabilities of occurrence of the high event times that of the low event. Furthermore, we observed modified channel openings after a normal opening for the two conductance channels and a modified one turning into a normal one for the high-conductance channel. It is concluded that veratridine induces the two different types of modified Na+ channels in cardiac myocytes and these are correlated with normal openings.
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
A
A
Sunami
T
T
Sasano
A
A
Matsunaga
Z
Z
Fan
T
T
Swanobori
M
M
Hiraoka
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006352:Heart Ventricles; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*
D015222:Sodium Channels; D013779:Tetrodotoxin; D014701:Veratridine; D002118:Calcium