Transient inward current is conducted through two types of channels in cardiac Purkinje fibres.
Two-microelectrode voltage-clamp technique was applied and a number of experimental manoeuvres were used to determine the charge-carrying systems of the arrhythmogenic transient inward current (TI) in rabbit cardiac Purkinje fibres. Increasing [Ca2+]o to 30 mmol/l (in the presence of [Na+]o) induced TI with a clear-cut reversal potential around -23 mV. This observation suggests that the TI is conducted through an ionic channel. Nickel chloride (2.5 mmol/l) which blocks Na+/Ca2+ exchange current greatly decreased peak inward TI (57 +/- 3%) but significantly increased peak outward TI (86.4 +/- 9.6%), which suggests that Na+ Ca2+ exchange is not the charge-carrying system for TI. In experiments in which TI was induced when [Na+]o was replaced by either N-methyl-D-glucamine, choline, or sucrose (to eliminate Na+ Ca2+ exchange), Ni2+ still decreased inward TI and increased outward TI. There was no significant difference between the effects of Ni2+ in the presence and absence of [Na+]o. The effects of Ni2+ in the absence of [Na+]o confirm that Ni(2+)-induced attenuation of inward TI is not mediated by the Na+ Ca2+ exchange, but rather through an inhibition of TI channels. Acute exposure to Mn2+ (5 mmol/l) almost abolished inward TI at a time when outward TI just showed a slight decrease. A third divalent cation, Cd2+ (0.25-1.0 mmol/l), strongly suppressed both inward and outward TI at the same time. The opposite effects of Ni2+ on inward v outward TI and the preferential inhibition of inward TI by Mn2- suggest involvement of multiple ionic channels in conducting TI. 4.4'-diisothiocyanatostilbene-2.2' disulfonic acid (DIDS, 10 mumol/l) and 4-acetamido-4'-isothicyanatostilbene-2.2' disulfonic acid (SITS. 0.2 mmol/l), which block CI- conductance in cardiac tissues, dramatically suppressed outward TI (80 +/- 9%) but to a lesser extent inward TI (20 +/- 4%). Our results suggest that, in cardiac Purkinje fibres, high [Ca2+]o induced TI is conducted mainly through TI channels which fall into two different populations: cationic and anionic.
Han
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Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrier
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D004553:Electric Conductivity; D007474:Ion Exchange; D019216:Metals, Heavy / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000502:physiology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*
D018118:Chloride Channels; D019216:Metals, Heavy; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium