Chloride‐sensitive nature of the adrenaline‐induced current in guinea‐pig cardiac myocytes.

Abstract

SUMMARY1. Ionic selectivity of an adrenaline-induced current was investigated in single guinea-pig ventricular cells by recording whole-cell currents using the patch clamp technique combined with internal perfusion. Other ionic currents and exchange currents known in ventricular cells were suppressed by appropriate inhibitors and the adrenaline-induced current was defined as a difference between currents obtained in the presence and absence of adrenaline.2. The adrenaline-induced current was time independent and its I-V relation showed saturation of the inward current in the negative voltage range.3. The reversal potential was approximately -20 mV with 140 mM-NaCl external solution and Cs+-rich internal solution containing 51 mM-Cl-. Replacing Na+ with various monovalent and divalent cations (Li+, K+, Rb+, Cs+, Ca2+, Sr2+ and Ba2+) produced no appreciable change in the reversal potential. 5. Anion substitutions did not appreciably affect the I-V relation before application of adrenaline, suggesting that the cell membrane had a low Clconductance in the control state.6. 4,4'-Dinitrostilbene-2-2'-disulphonic acid (DNDS; 1-10 mM), a specific inhibitor of membrane chloride permeability, depressed the adrenaline-induced current without changing the reversal potential.7. The results suggest strongly that the adrenaline-induced current is carried mainly by Cl-. However, the development of this current appears to depend also on external cations, since the magnitude of the adrenaline response varied depending on the external cation species, with no response in Tris-HCl or TEA-Cl solution. The external cations may facilitate the adrenaline response with a sequence of efficacy of Na+ > K+, Rb+ > Cs+, Li+, divalent cations. t Present address:

Modulation by histamine of the delayed outward potassium current in guinea‐pig ventricular myocytes

“…Secondly, the holding potential is concerned with the (Bahinski et al, 1989;Harvey & Hume, 1989;Matuoka et al, 1990). The reversal potential for this current depends on the external and internal Cl-concentrations.…”

Exponential activation of the cardiac Na+ current in single guinea‐pig ventricular cells.

“…Using the model of the oil gap, composed of the membrane capacitance and resistance distributed along the cell axis in both the oil gap and the external compartment (cable theory: Cole & Curtis, 1938;Hodgkin & Rushton, 1946; see also Ishihara et al 1989), the resistance of the water layer around the cell within the oil gap was calculated. If a membrane conductance of 25 pS/pF was used, which is that found in the absence of the inward rectifier K+ current (Matsuoka, Ehara & Noma, 1990), a total membrane conductance of 1000-1250 pS was obtained, which gives a resistance of 0-8-1-0 GQ. An intracellular axial resistance of 104 MQ/cm was assumed.…”

Functionally distinct phospho-forms underlie incremental activation of protein kinase-regulated Cl- conductance in mammalian heart.

“…In the myocardium, ~-adrenergic agonists regulate a variety of ionic currents (for reviews, see Hartzell, 1988;Gadsby, 1990), including a CI-current identified recently in guinea pig and rabbit ventricular myocytes (Harvey and Hume, 1989;Bahinski, Nairn, Greengard, and Gadsby, 1989b;Matsuoka, Ehara, and Noma, 1990). Activation of that CI-conductance requires phosphorylation by cAMP-dependent protein kinase (PKA) because the CI-conductance can be elicited by direct intracellular application of either cAMP or the catalytic subunit of PKA (Bahinski et al, 1989b), and it can be abolished (Bahinski, Gadsby, Greengard, and Nairn, 1989a;Hwang, Horie, Nairn, and Gadsby, 1992c) by intracellular application of a specific peptide inhibitor of PKA (PKI; i.e., Walsh inhibitor, 5-24-amide; Cheng, Kemp, Pearson, Smith, Misconi, Van Patten, and Walsh, 1986).…”