K + currents regulate function in ventricular fibroblasts and myofibroblasts

Abstract

Fibroblasts and myofibroblasts have essential roles in the formation and maintenance of the extracellular matrix in mammalian hearts. Electronic coupling between fibroblasts, and between fibroblasts and myocytes have been demonstrated and connexin isoforms have been detected. Whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts from rat hearts. Time- and voltage-dependent outward K+ currents were recorded at depolarized potentials, and an inwardly rectifying K+ (Kir) current was identified near the resting membrane potential. The rapidly activating K+ current in response to large depolarizations resembles Kv1.6. RT-PCR measurements showed that mRNA for Kir 2.1 and Kv 1.6 was expressed. Changes in [K+]o alter fibroblast membrane potential as well as proliferation and contractile function. Recordings made with a voltage-sensitive dye, DiBAC3(4), showed that 1.5 mM [K+]o resulted in hyperpolarization, whereas 20 mM[K+]o produced depolarization. In separate assays, 20mM [K+]o significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with the control mechanical activity in 5.4 mM [K+]o. These results show that ventricular fibroblasts and myofibroblasts express a variety of K+ channel alpha subunits, and demonstrate that Kir current can modulate RMP and alter essential physiological functions. Some of the consequences of electrotonic coupling of fibroblasts and myofibroblasts to ventricular myocytes can be illustrated using mathematical models of these types of cells.