Ionic mechanisms of transient inward current in the absence of Na(+)‐Ca2+ exchange in rabbit cardiac Purkinje fibres.

Abstract

was shifted to -12-5 and + 5 mV, respectively. The peak outward TI was also greatly suppressed when [Cl-]0 was decreased. The magnitude of peak inward TI was not significantly different with either choline chloride or sucrose substitution.7. Two anion transporter blockers, 4,4'-diisothiocyanatostilbene-2,2'disulphonic acid (DIDS) and 4-acetamide-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS), which are known to block the Cl-conductance in cardiac tissues, abolished outward TI at a concentration of 10 AUM for DIDS and 0-1 to 0-2 mm for SITS.8. Our results indicate that the TI can occur in the absence of Na+-Ca2+ exchange in rabbit cardiac Purkinje fibres. In addition, under the present experimental conditions, the TI is carried by two components: (1) a Ca2+-activated cationic component which is primarily responsible for inward TI (i.e. rectifies inwardly); (2) a Ca2+-activated Cl-conductance that accounts for most or all of the outward TI, but which also contributes to inward TI. A balance of cation and anion conductances determine the magnitude of the TI plus the occurrence and value of a reversal potential.

Two components of [Ca2+]i‐activated Cl‐ current during large [Ca2+]i transients in single rabbit heart Purkinje cells.

“…Therefore, direct comparison with our results remains difficult. Our results are, however, consistent with the observation by Han & Ferrier (1992) …”

“…However, large and slow [Ca2+]i-dependent currents were recently described during [Ca2+]i overload in multicellular Purkinje fibres studied with dual microelectrode voltage clamp (Han & Ferrier, 1992). In this preparation, outward currents and a small fraction of the inward currents were ascribed to Cl-currents.…”

Calcium‐activated transient membrane currents are carried mainly by chloride ions in isolated atrial, ventricular and Purkinje cells of rabbit heart

“…Since then the calcium ion dependence of this Cl-component has been documented by several authors (e.g. Zygmunt & Gibbons, 1991;Sipido, Callewaeert & Carmeliet, 1993) (Mechmann & Pott, 1977) and chick embryonic heart cells (Clusin, 1983;Clusin, Fischmeister & DeHaan, 1983) to caffeine also elevated the myoplasmic calcium ion concentration ([Ca2+] (Kass, Tsien & Weingart, 1978b;Colquhoun, Neher, Reuter & Stevens, 1981;Cannell & Lederer, 1986;Ehara, Noma & Ono, 1988;Han & Ferrier, 1992) or (2) a [Ca2+]1-modulated, electrogenic Na'-Ca2+ exchanger ; Arlock & Katzung, 1985;Beuckelmann & Wier, 1989). More recently, however, the involvement of Icl(ca) in ITI generation (Zygmunt, 1994;Papp, Sipido, Callewaert & Carmeliet, 1995;Laflamme & Becker, 1996;Collier, Levesque, Kenyon & Hume, 1996) has been suggested.…”

“…Non-selective cation currents have been described mainly in single channel experiments (Ehara et al 1988) but they have also been demonstrated in multicellular preparations (Cannel & Lederer, 1986;Han & Ferrier, 1992), where direct control of the composition of intra-and extracellular spaces was difficult. In the present study, where such technical limitations are less likely to be encountered, we were unable to demonstrate the activation of a non-specific cationic membrane conductance.…”

“…In these studies Ca2+ transients were elicited by Ca2+-induced Ca2' release from the sarcoplasmic reticulum during depolarizing voltage steps, which are known to elevate [Ca2 ]i in a homogeneous manner. Outward Cl-currents of longer duration have been also postulated to contribute to membrane currents during after-contractions in Ca2+-overloaded multicellular Purkinje preparations (Han & Ferrier, 1992) and ventricular cells (Laflamme & Becker, 1996). In isolated Purkinje cells, brief caffeine applications demonstrated the reversal of two kinetically distinct components of the [Ca2+]1-activated Cl-current seen during single Ca2+ transients (Papp et al 1995 (Uchida et al 1993).…”