Abstract

We tested hypotheses concerning the muscarinic receptor subtype and the involvement of L-type Ca current (I_Ca) in the stimulation of contractions by carbachol (CCh) in single guinea pig ventricular myocytes. When superfused with Tyrode’s solution (36°C, 5.4 mM [Ca⁺⁺]_o) and stimulated at 0.2 Hz, CCh (EC₅₀ ≈18 μM) increased the early component of isotonic contractions by acting at muscarinic receptors indistinguishable from the M₂ subtype because AF-DX 116 (M₂-selective) was more potent than pirenzepine (M₁-selective) as an antagonist of the CCh effect. Action potential duration decreased slightly and I_Ca was not increased when CCh increased contractions. Carbachol increased intracellular Ca⁺⁺transients and contractions reversibly, which indicated an effectvia sarcoplasmic reticulum (SR) Ca stores. Ryanodine (1–10 μM) blocked the early contraction component increased by CCh, another indication that CCh action depends on SR Ca stores. We previously found that CCh increased a background Na⁺current by occupancy of M₂ receptors. We now report that the increased contractions by CCh can also originate at M₂receptors and that SR Ca stores are involved in the CCh effect. Because CCh did not significantly increase I_Ca, the initial increase of intracellular Na⁺ by CCh may eventually act through Na-Ca exchange to enhance excitation-contraction coupling.