SWELLING-ACTIVATED AND ISOPRENALINE-ACTIVATED CHLORIDE CURRENTS IN GUINEA-PIG CARDIAC MYOCYTES HAVE DISTINCT ELECTROPHYSIOLOGY AND PHARMACOLOGY

We have used the whole-cell patch clamp recording technique to charact erize a swelling-activated chloride current in guinea pig atrial and v entricular myocytes and to compare the electrophysiological and pharma cological properties of this current with the isoprenaline-activated c hloride current in the same cell types. Osmotic swelling of guinea pig cardiac myocytes caused activation of an outwardly rectifying, anion- selective current with a conductance and permeability sequence of I- s imilar to NO3- > Br- > Cl- > Asp(-). This current was inhibited by tam oxifen, 4,4'-diisothiocyano-stilbene-2,2'-disulphonate and anthracene- 9-carboxylic acid, in decreasing order of potency. The isoprenaline-ac tivated anion current, like the swelling-activated current, had a high er permeability to I- relative to Cl-, but it had a markedly reduced c onductance for I- compared to Cl-. The isoprena line-activated current was insensitive to inhibition by tamoxifen, 4,4'-diisothiocyano-stilb ene-2,2'-disulphonate and anthracene-9-carboxylic acid. The swelling-a ctivated current could be elicited in > 90% atrial myocytes studied bu t only 34% ventricular myocytes. Conversely, the isoprenaline-activate d current was elicited in < 10% atrial myocytes and > 90% ventricular myocytes. In those ventricular myocytes where it was possible to elici t swelling-activated and isoprenaline-activated currents simultaneousl y, the currents retained the same distinguishing characteristics as wh en they were elicited in isolation. Thus, while guinea pig atrial cell s appear to preferentially express swelling-activated chloride channel s and guinea pig ventricular myocytes preferentially express isoprenal ine-activated chloride channels, the presence of these two channel typ es are not necessarily mutually exclusive. This raises the possibility that there may be coordinated regulation of the expression of differe nt CI- channels within the heart.