Swelling-activated and isoprenaline-activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology

Abstract

We have used the whole-cell patch clamp recording technique to characterize a swelling-activated chloride current in guinea pig atrial and ventricular myocytes and to compare the electrophysiological and pharmacological properties of this current with the isoprenaline-activated chloride 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- ~ NO3/- > Br- > Cl- > Asp-. This current was inhibited by tamoxifen, 4,4'- diisothiocyano-stilbene-2,2'-disulphonate and anthracene-9-carboxylic acid, in decreasing order of potency. The isoprenaline-activated anion current, like the swelling-activated current, had a higher permeability to I- relative to Cl-, but it had a markedly reduced conductance for I- compared to Cl-. The isoprenaline-activated current was insensitive to inhibition by tamoxifen, 4,4'-diisothiocyano-stilbene-2,2-disulphonate and anthracene-9- carboxylic acid. The swelling-activated current could be elicited in >90% atrial myocytes studied but only 34% ventricular myocytes. Conversely, the isoprenaline-activated current was elicited in < 10% atrial myocytes and >90% ventricular myocytes. In those ventricular myocytes where it was possible to elicit swelling-activated and isoprenaline-activated currents simultaneously, the currents retained the same distinguishing characteristics as when they were elicited in isolation. Thus, while guinea pig atrial cells appear to preferentially express swelling-activated chloride channels and guinea pig ventricular myocytes preferentially express isoprenaline-activated chloride channels, the presence of these two channel types are not necessarily mutually exclusive. This raises the possibility that there may be coordinated regulation of the expression of different Cl- channels within the heart. Show more